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288
Structure and function of proteins controlling strain-specific
pathogen resistance in plants
Jeff Ellis∗ and David Jones†
Recently recognised structural and amino acid sequence
similarities between plant disease resistance (R) proteins
and animal proteins such as Apaf-1 and CED-4 are providing
conceptual models for resistance protein function. Data from
extensive DNA sequencing of resistance gene families are
indicating that the leucine-rich repeat motif is an important
determinant of gene-for-gene specificity and that intergenic
DNA sequence exchange is a major contributor to R gene
diversity.
Addresses
∗CSIRO Plant Industry, GPO Box 1600, Canberra ACT 2601,
Australia; e-mail: ellisj@pi.csiro.au
†Research School of Biological Sciences, Australian National
University, PO Box 475, Canberra ACT 2601, Australia; e-mail:
jones@rsbs.anu.edu.au
Current Opinion in Plant Biology 1998, 1:288–293
http://biomednet.com/elecref/1369526600100288
Current Biology Ltd ISSN 1369-5266
Abbreviations
avr
avirulence
IL-1
interleukin-1
LRR
leucine-rich repeat
NBS
nucleotide binding site
PK
protein kinase
R
resistance
TM
transmembrane domain
TIR
Toll and IL-1 receptor
Introduction
Highly polymorphic plant genes (R genes) that control
specific disease resistance [1•], encode proteins in several
classes, some of which bear the hallmarks of innate
immunity and cell death proteins in animals. These
proteins function in surveillance systems for pathogens,
probably detecting pathogen-encoded avirulence gene
products which in other contexts may function as virulence
factors (see [2••] for an excellent example).
Recent reviews (e.g. [1•]) have extensively covered the
comparisons and classification of predicted plant disease
resistance gene products (R proteins) which incorporate
several common structural themes: nucleotide binding
sites (NBSs), leucine-rich repeats (LRRs), transmembrane
domains (TMs) and serine/threonine protein kinases
(PKs). These are combined in several arrangements with
the following signatures, NBS-LRR, LRR-TM-PK, LRRTM and PK. An additional and novel class containing the
Hs1pro-1 nematode resistance protein is discussed in this
review. The largest number of characterised R proteins
are in the NBS-LRR class and so far, proteins in this
class have no other known functions apart from disease
resistance. Similarities between the NBS domain of these
proteins and animal proteins regulating apoptosis (detailed
below), however, suggest that researchers be mindful of
the possibility that some NBS-LRR proteins may function
in plant developmental processes involving programmed
cell death. One example of a ‘multiskilled’ family of
proteins is the LRR-TM-PK class. Although Xa21 is the
only resistance protein in this class, several plant protein
‘relatives’ involved in developmental control and hormone
perception have now been identified, suggesting that Xa21
may have been ‘recruited’ for pathogen detection.
Hs1pro-1: an unusual resistance gene
The predicted protein encoded by the recently cloned
Hs1pro-1 gene for nematode resistance in sugar beet was
reported to have an LRR-TM signature [3], but our
analysis indicates that it does not appear to fit this or
any other of the existing R protein structural signatures.
For example, database searches show no homology to any
previously analysed R gene or LRR protein. Additionally,
the proposed signal peptide and TMs of Hs1pro-1 are
very short and contain a number of charged or polar
residues inconsistent with such roles. Furthermore, the
proposed LRR domain lacks the features of any LRR
consensus that has been described to date, not only
with respect to the spacing of the leucines, but also
regarding the absence of distinctive non-leucine residues.
An Arabidopsis homologue (GenBank accession G2088653)
has been described that was predicted to have a more
extensive amino-terminal domain than Hs1pro-1, but this
shows no better similarity to the LRR-TM signature.
Hs1pro-1 seems likely, therefore, to represent the first
member of an entirely new class of R genes encoding a
novel cytoplasmic proteins.
Xa21: relatives in different professions
The Xa21 gene from rice confers resistance to Xanthomonas
oryzae pv. oryzae (Xoo) and encodes a protein with the
LRR-TM-PK signature in which the LRR is predicted to
be extracellular [4]. So far, Xa21 is the only R protein in
this class. PCR-based methods could provide the means
to clone more R genes in this class, however, this is
clearly not a direct route now that several other plant
genes have been cloned which encode LRR-TM-PK
proteins apparently not involved in pathogen resistance.
These include developmental genes like ERECTA [5]
and CLAVATA1 [6] of Arabidopsis and SERK [7] of carrot,
and the gene encoding a putative brassinosteroid receptor
(BRI) [8] of Arabidopsis. Thus, this class of protein fulfils
several roles in plants. The LRR domain might detect
extracellular ligands of various types, including potentially
Structure and function of proteins controlling strain-specific pathogen resistance in plants Ellis and Jones
the product of the avrXa21 avirulence gene of Xoo.
The involvement of the LRR region of this class in
ligand recognition, however, has not been experimentally
demonstrated and so it is possible that the PK domain of
Xa21, like that of the tomato bacterial resistance protein
Pto which contains only the PK domain [9,10], detects the
corresponding Avr protein.
Xa1, a second rice gene for resistance to Xoo strains
carrying avirulence gene avrXa1, has recently been cloned
and in contrast to Xa21, found to encode a NBS-LRR
protein [11•]. Thus, two unrelated classes of R protein
are used in rice to perceive the same pathogen species
(but different avr genes!). The NBS-LRR proteins
are predicted to be intracellular, whereas the LRR
domain of Xa21 is predicted to be extracellular [12•].
The LRR domains of Xa1 and Xa21, assumed to be
involved in avr ligand binding, are therefore in different
subcellular locations. The cloning and comparison of the
corresponding avr genes, avrXa1 and avrXa2, from Xoo is
keenly anticipated to determine whether the nature and
delivery of the avr ligands reflects these locations.
NBS-LRR resistance proteins: strength in
numbers
The NBS-LRR class is by far the largest group of
resistance proteins. Two subgroups within the NBS-LRR
class have been recognised by the presence or absence
of an amino-terminal region (TIR domain) with amino
acid sequence similarity and predicted structural similarity
[13•,14,15] to the cytoplasmic signalling domains of
the Toll and interleukin-1 (IL-1) receptor. The first
subgroup (TIR-NBS-LRR) includes N (tobacco mosaic
virus resistance, [1•]), L6 (flax rust resistance [1•]), M
(flax rust resistance [16•]) and RPP5 (downy mildew
resistance [13•]). Furthermore, the involvement of plant
and animal TIR proteins in defence processes [15–19]
indicates that they may have their origins in a very ancient
defence mechanism. Recent advances in understanding
the role of Toll and IL-1R in defence processes provide
additional clues about the role of the plant TIR domain.
In Toll/IL-1R signalling, the cytoplasmic TIR domains
are involved in the activation of the PKs Pelle/IRAK
and IRAK-2 via the protein intermediaries Tube/IL-1AcP
and MyD88 [20–23]. Interestingly, MyD88 has an adaptor
protein with an amino-terminal domain similar to those of
IRAK and IRAK-2 and a carboxy-terminal TIR domain
similar to those of IL-1R and IL-1AcP. Heterodimerisation
via the TIR domains on one hand and the amino terminal
domains on the other, might enable MyD88 to act as an
adaptor linking the upstream and downstream components
of the signal transduction process in IL-1R signalling
[21–23]. TIR domains, however, have yet to be detected
among any plant proteins other than the TIR-NBS-LRR
class.
The second subgroup, which lacks the TIR region,
includes the bacterial resistance proteins RPS2, RPM1
289
[1•], Xa1 [11•], Prf [24], the fungal resistance protein I2
[25•] and the possible nematode resistance protein Cre3
[26•]. Of this subgroup, RPS2, RPM1 and Prf are predicted
to contain an amino-terminal leucine zipper (LZ), a motif
frequently involved in protein dimerization. Whether this
motif is functional in dimerisation of R proteins has not
yet been reported and no homologous animal system
with extended similarity in the LZ domain has emerged
upon which to model the function of this domain. The
interaction between this domain and the LZ domain of a
downstream signalling component in a pathway distinct to
that used by the TIR-NBS-LRR subclass seems plausible,
however. Recent genetic evidence indicates that proteins
in these two classes signal through different pathways.
In Arabidopsis, proteins in the TIR class signal via a
pathway that includes EDS1 ([27]; JE Parker, personal
communication) and proteins in the LZ class signal
through a pathway that includes the recently cloned NDR1
gene ([28•]; BJ Staskawicz, personal communication).
Both NDR1 and EDS1 were identified by mutation
screens for loss of disease resistance [27,28•]. There is
no apparent correlation between pathogen type (virus,
fungus, bacterium etc.) and the NBS-LRR subclass used
by plants to detect these pathogens.
NBS-LRRs: the nucleotide binding domain,
an apoptosis connection and a model for
function
Database searches have consistently failed to identify NBS-LRR organisation in bacteria, yeast or animal
genomes. Recently, however, clear and extensive amino
acid sequence similarity in the NBS domain, including
motifs that were previously thought to be common only to
plant NBS-LRR proteins, has been detected in nematode
CED-4 and mammalian Apaf-1 proteins — activators of
the apoptotic proteases CED-3 and caspase-9 respectively
[29•,30••]. One common, but not necessarily universal, feature of NBS-LRR function is the occurrence
of hypersensitive cell death at infection sites during
resistance reactions. The similarity between this response
and animal apoptosis has often been remarked upon, so
this structural similarity between the NBS-LRR proteins
and CED-4 and Apaf-1 is intriguing. Experimental
evidence for nucleotide binding at the NBS site has been
obtained for CED-4 [30••] and for the RPS2 resistance
protein (A Bent, personal communication), suggesting
a functional similarity. CED-4 and Apaf-1 appear to
act as adaptor molecules with a central NBS domain
and an amino-terminal effector domain [30••,31]. The
carboxy-terminal receptor domain of Apaf-1 is composed
of repeating amino acid motifs, designated WD-40 repeats,
involved in protein–protein interactions (analogous to
the LRR domain) [31]. Interestingly, both CED-4 and
Apaf-1 appear to activate their target proteases (CED-3
and caspase-9 respectively) by heterodimerisation of
homologous amino-terminal domains present in both the
activators and the proteases [30••,32]. This is reminiscent
of the interaction between homologous domains of MyD88
290
Plant–microbe interactions
and other components of the IL-1R system discussed
above and encourages a search for plant proteins that may
interact through homology with the TIR or LZ domains
of resistance proteins.
Many NBS-LRR plant genes have been identified through
plant genome sequencing projects [33] and by PCR
using redundant primers based on NBS motifs [34–37].
Programmed cell death is used in plant developmental
processes and the question arises whether any of these
newly identified NBS-LRRs lacking ascribed resistance
function may have a role in development rather than
resistance.
Resistance genes at complex loci
Genetic mapping of resistance gene specificities has
indicated that they frequently cluster at complex loci.
Sequence data now show that such loci represent all
classes of R genes except Hs1pro-1, and contain tandem
arrays of closely related genes [25•,38,39••,40•]. The
tomato Cf-4/9 locus (LRR-TM class) from two lines (Cf4
and Cf9) and the tomato Pto locus (PK class) contain
multiple genes, most of which appear to be functional
[38], while the rice Xa21 locus (LRR-TM-PK class) [40•]
and the Arabidopsis RPP5 locus (TIR-NBS-LRR class)
from ecotype Col-O [41] contain a high proportion of
pseudogenes, with several carrying transposons, deletions
or frame shifts. These arrays of paralogous genes may
provide a means of maintaining favourable haplotypes
with multiple specificities or may act as reservoirs of
sequence diversity for generating new specificities by
intergenic sequence exchange. In contrast, members of the
LRR-TM-PK class mentioned above as developmental
regulators or hormone receptors occur as single genes at
simple loci. The latter proteins are likely to be focused
on single ligands that are evolutionarily stable in contrast
to rapidly changing pathogen ligands. Simple R gene loci
also exist and in at least one case, the L rust resistance
locus in flax, diversity is provided by a multiply allelic
series. In a number of cases, however, such as RPS2
[1•], RPM1 [1•], and Xa1 [11•], the R genes exist as
single genes at simple loci with only a single recognitional
specificity. Furthermore, complexity at a particular locus
can be variable; for example, only a single gene occurs
at the Cf-4/9 locus in the susceptible Cf0 line of tomato
[39••], probably reflecting deletion events resulting from
unequal crossing over at an ancestral complex locus.
Resistance gene specificity
All of the R genes discussed in this review show a high
level of recognitional specificity, that is, they provide resistance against only some strains of a particular pathogen
species. This is principally the result of a high level of
polymorphism among pathogen avirulence genes which
encode the probable ligands of the resistance protein
receptors. This contrasts with our current perception of the
innate immunity systems in Drosophila where specificity is
manifest against common ligands within pathogen classes,
for example, Gram-positive or Gram-negative bacteria or
fungal pathogens [42].
Three systems are currently providing insight into the
molecular basis of specificity in pathogen strain recognition. In the interaction between the tomato Pto and
Pseudomonas syringae AvrPto proteins, domain swap experiments between Pto and another closely related gene, Fen,
at the complex Pto locus and yeast two-hybrid analysis
of the chimeric genes have identified a small region of
Pto involved in the interaction with AvrPto and thus
also involved in the determination of specificity towards
races of P. syringae carrying the avrPto gene [9,10]. In the
second system, also in tomato, 11 homologous genes at the
Cf-4/9 locus for Cladosporium fulvum resistance have been
sequenced [39••]. Comparison of the predicted amino
acid sequences shows conservation in the carboxy-terminal
halves of the proteins, which include about a third of the
LRRs; an extreme example being complete identity in
the carboxy-terminal halves of the Cf-4 and Cf-9 proteins
[43•]. This implies that the specificity of recognition
of avirulence ligands is determined by the LRRs of
the variable amino-terminal regions. These comparisons
also show that variation within the amino-terminal LRR
region occurs predominantly in regions predicted to form
a solvent-exposed parallel sheet and thought to provide a
platform for the presentation of nonconserved residues for
specific interaction with protein ligands [12•].
Analysis of the nucleotide sequence of these 11 homologues revealed variation originating from mutation, segmental exchange between adjacent homologues within
tandem arrays (either by repeated rounds of unequal
exchange or by gene conversion) and duplication or
deletion of complete LRR units; for example, Cf-4 differs
from Cf-9 by a precise deletion of two complete LRRs
[43•]. The predicted parallel β-sheet arrangement of LRRs
means that a given amino acid has both a horizontal
context — the neighbouring amino acids within its own
LRR unit, and a vertical context — amino acids in a similar
position in the two flanking LRRs. Segmental exchange,
although it may have had a limited role in producing
novel combinations in the horizontal context, would seem
to have had a more important role in producing novel
combinations of amino acids in the vertical context.
Deletion and duplication of LRRs would have the same
effect.
In the third system, the predicted protein sequences of
13 active alleles of the flax L gene (TIR-NBS-LRR)
conferring rust resistance [44•] are over 90% identical
but show variation over the entire length of the protein.
The greatest sequence variation is observed in the LRR
region. The same three sources of variation acting on the
Cf genes also appear to operate for LRR domains of the
L alleles. Selection seems to be acting in a similar way
to favour diversification in the potential strand regions
and conservation in the nonstrand regions of the LRR
Structure and function of proteins controlling strain-specific pathogen resistance in plants Ellis and Jones
domain. Sequence comparisons and interallelic domain
swap experiments, however, also indicate that the aminoterminal TIR domain makes important contributions to
allelic specificity in addition to the LRR domain (J Ellis et
al., unpublished data).
4.
Song W-Y, Wang G-L, Chen L-L, Kim H-S, Pi L-Y, Holsten T,
Gardner J, Wang B, Zhai W-X, Zhu L-H et al.: A receptor kinaselike protein encoded by the rice disease resistance gene,
Xa21. Science 1995, 270:1804-1806.
5.
Torii KU, Mitsukawa N, Oosumi T, Matsuura Y, Yokoyama R,
Whittier RF, Komeda Y: The Arabidopsis ERECTA gene encodes
a putative receptor protein kinase with extracellular leucinerich repeats. Plant Cell 1996, 8:735-746.
6.
Clark SE, Williams RW, Meyerowitz EM: The CLAVATA1 gene
encodes a putative receptor kinase that controls shoot and
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7.
Schmidt EDL, Guzzo F, Toonen MAJ, de Vries SC: A leucinerich repeat containing receptor-like kinase marks somatic
plant cells competent to form embryos. Development 1997,
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8.
Li J, Chory J: A putative leucine-rich repeat receptor kinase
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9.
Scofield SR, Tobias CM, Rathjen JP, Chang JH, Lavelle DT,
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Conclusions
The number of cloned R genes is rapidly increasing and genetic and molecular studies have identified
several downstream signalling components in resistance
[27,28•,45•]. One example of a strain-nonspecific resistance gene, mlo, has been cloned [46•] and analysis and
engineering of the homologues in other plant species may
lead to further examples of ‘broad spectrum resistance’.
Basic information concerning how these genes function
is appearing more slowly, but genomic and comparative
studies are providing leads. In only one example (Avr Pto
and Pto [9,10]) has evidence of direct interaction between
a resistance and avirulence protein been reported, in
spite of the fact that several other cloned bacterial
and fungal avirulence genes corresponding to cloned
resistance genes are available. The possibility remains
that these interactions will involve one or more additional
host proteins as in the animal apoptosome complex
which involves Apaf-1, Bcl-2 and Caspase 3 [29•]. Many
avirulence genes corresponding to cloned resistance genes
are yet to be cloned and no X-ray crystallographic analysis
of R proteins has been reported. Thus several critical areas
of ignorance are ripe for illumination in the near future.
References and recommended reading
Papers of particular interest, published within the annual period of review,
have been highlighted as:
• of special interest
•• of outstanding interest
1.
Hammond-Kosack KE, Jones JDG: Plant disease resistance
•
genes. Annu Rev Plant Physiol Plant Mol Biol 1997, 48:575-607.
An extensive review of cloned plant disease resistance genes and comparison of their products.
2.
••
Bogdanove AJ, Kim JF, Wei Z, Kolchinsky P, Charkowski AO,
Conlin AK, Collmer A, Beer SV: Homology and functional
similarity of an hrp-linked pathogenicity locus, dspEF,
of Erwinia amylovora and the avirulence locus avrE of
Pseudomonas syringae pathovar tomato. Proc Natl Acad Sci
USA 1998, 95:1325-1330.
The function of pathogen avirulence genes has been enigmatic. Several
examples among plant bacterial pathogens have indicated that avirulence
gene mutants have decreased virulence. This paper describes two dspEF
genes in the apple fireblight pathogen Erwinia that encode factors necessary
for virulence. When transferred and expressed in Pseudomonas syringae,
however, they function as avirulence genes and induce defence responses
in specific resistant lines of soybean. Avirulence genes with high sequence
similarity are also identified in P. syringae and these genes can complement
dspEF mutants in Erwinia. These data provide strong support for the view
that avirulence genes encode virulence factors for which host genotypes
have evolved specific surveillance mechanisms. Furthermore, they suggest
the intriguing possibility of isolating resistance genes from soybean which
have the appropriate specificity to protect apple (for which no fireblight R
genes are known) from this disease.
3.
Cai D, Kleine M, Kifle S, Harloff H-J, Sandal NN, Marcker KA,
Klein-Lankhorst RM, Salentijn EMJ, Lange W, Stiekema WJ et al.:
Positional cloning of a gene for nematode resistance in sugar
beet. Science 1997, 275:832-834.
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•
Yoshimura S, Yamanouchi U, Katayose Y, Toki S, Wang Z-X, Kono
I, Kurata N, Yano M, Iwata N, Sasaki T: Expression of Xa1, a
bacterial blight-resistance gene in rice, is induced by bacterial
inoculation. Proc Natl Acad Sci USA 1998, 95:1663-1668.
The map-based cloning of a second blight resistance gene in rice is described and the amino acid sequence predicted. The predicted product contains six near perfect 93 amino acid repeats in the LRR region and Xa1 expression is induced by infection and wounding. Whether any other R genes
are induced has not been addressed in any detail in previous publications.
12.
Jones DA, Jones JDG: The role of leucine-rich repeat proteins
•
in plant defences. Adv Bot Res 1997, 24:89-167.
An extensive review of plant LRR proteins and discussion of features that
may be used to predict whether these proteins are intracellular or extracellular.
13.
•
Parker JE, Coleman MJ, Szabo V, Frost LN, Schmidt R, van
der Biezen E, Moores T, Dean C, Daniels MJ, Jones JDG: The
Arabidopsis downy mildew resistance gene RPP5 shares
similarity to the Toll and Interleukin-1 receptors with N and L6.
Plant Cell 1997, 9:879-894.
Like [16•] this paper describes a deletion event involving repeated sequence
elements in the leucine-rich repeat region and indicates that these events
may play a role in the evolution of the genes.
14.
Baker B, Zambryski P, Staskawicz B, Dinesh-Kumar SP: Signaling
in plant-microbe interactions. Science 1997, 276:726-733.
15.
Rock FL, Hardiman G, Timans JC, Kastelein RA, Bazan JF: A
family of human receptors structurally related to Drosophila
Toll. Proc Natl Acad Sci USA 1998, 95:588-593.
16.
•
Anderson PA, Lawrence GJ, Morrish BC, Ayliffe MA, Finnegan
EJ, Ellis JG: Inactivation of the flax rust resistance gene M
associated with the loss of a repeated unit within the leucinerich repeat coding region. Plant Cell 1997, 9:641-651.
A description of the TIR-NBS-LRR (Toll and Interleukin 1 receptor-nuclear
binding site-leucine rich repeat) flax rust resistance gene M and of mutants
that arise by intragenic events involving two direct repeats in the LRR. It compares M with L6, two highly related products with different rust resistance
specificity, the former being encoded by a complex tandem array of genes
and the latter by a single gene with multiple alleles at a simple locus.
17.
Lemaitre B, Nicolas E, Michaut L, Reichhart J-M, Hoffmann JA:
The dorsoventral regulatory gene cassette spätzle/Toll/cactus
controls the potent antifungal response in Drosophila adults.
Cell 1996, 86:973-983.
292
Plant–microbe interactions
18.
Williams MJ, Rodriguez A, Kimbrell DA, Eldon ED: The 18-wheeler
mutation reveals complex antibacterial gene regulation in
Drosophila defense. EMBO J 1997, 16:6120-6130.
19.
Medzhitov R, Preston-Hurlburt P, Janeway CA: A human
homologue of the Drosophila Toll protein signals activation of
adaptive immunity. Nature 1997, 338:394-397.
20.
Yang J, Steward R: A multimeric complex and the nuclear
targeting of the Drosophila rel protein dorsal. Proc Natl Acad
Sci USA 1997, 94:14524-14529.
21.
Muzio M, Ni J, Feng P, Dixit VM: IRAK (Pelle) family member
IRAK-2 and MyD88 as proximal mediators of IL-1 signaling.
Science 1997, 278:1612-1615.
22.
30.
••
Chinnaiyan AM, Chaudhary D, O’Rourke K, Koonin EV, Dixit VM:
Role of CED-4 in the activation of CED-3. Nature 1997,
338:728-729.
This paper was the first to draw attention to the amino acid similarities between the NBS regions of the nematode CED-4 protein and the L6 flax rust
resistance protein.
31.
Zou H, Henzel WJ, Liu XS, Lutschg A, Wang XD: Apaf-1, a
human protein homologous to C. elegans CED-4, participates
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90:405-413.
32.
Li P, Nijhawan D, Budihardjo J, Srinivasula SM, Ahmad M, Alnemri
ES, Wang XD: Cytochrome c and dATP-dependent formation
of Apaf-1/caspase-9 complex initiates an apoptotic protease
cascade. Cell 1997, 91:479-489.
Volpe F, Clatworthy J, Kaptein A, Maschera B, Griffin A-M, Ray
K: The IL1 receptor accessory protein is responsible for the
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the IL1/IL1 receptor I complex. FEBS Lett 1997, 419:41-44.
33.
Botella MA, Coleman MJ, Hughes DE, Nishimura MT, Jones JDG,
Sommerville SC: Map locations of 47 Arabidopsis sequences
with similarity to disease resistance genes. Plant J 1997,
12:1197-1211.
23.
Wesche H, Henzel WJ, Shillinglaw W, Li S, Cao ZD: MyD88 — an
adapter that recruits IRAK to the IL-1 receptor complex.
Immunity 1997, 7:837-847.
34.
Leister D, Ballvora A, Salamini F, Gebhardt C: A PCR-based
approach for isolating pathogen resistance genes from potato
with potential for wide applications in plants. Nat Genet 1996,
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24.
Salmeron JM, Oldroyd GED, Rommens CMT, Scofield SR, Kim
HS, Lavelle DT, Dahlbeck D, Staskawicz BJ: Tomato Prf is a
member of the leucine-rich repeat class of plant disease
resistance genes and lies embedded within the Pto kinase
gene cluster. Cell 1996, 86:123-133.
35.
Yu YG, Buss GR, Saghai-Maroof MA: Isolation of a superfamily
of candidate disease resistance genes from soybean based on
a conserved nucleotide binding site. Proc Natl Acad Sci USA
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36.
Kanazin V, Marek LF, Shoemaker RC: Resistance gene analogues
are conserved and clustered in soybean. Proc Natl Acad Sci
USA 1996, 93:11746-11750.
37.
Leister D, Kurth J, Laurie DA, Yano M, Sasaki T, Devos K, Graner
A, Schulze-Lefert P: Rapid reorganization of resistance gene
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38.
Jia Y, Loh Y-T, Zhou J, Martin GB: Alleles of Pto and Fen occur
in bacterial speck-susceptible and fenthion-insensitive tomato
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9:61-73.
25.
•
Ori N, Eshed Y, Paran I, Presting G, Aviv D, Tanksley S, Zamir
D, Fluhr R: The I2C family from the wilt disease resistance
locus I2 belongs to the nucleotide binding, leucine-rich repeat
superfamily of plant disease resistance genes. Plant Cell 1997,
9:521-532.
A family of R genes of the NBS-LRR class encoding Fusarium oxysporum
f.sp lycopersici resistance is described. The authors show that antisense
technology can be used to confirm that a cloned R gene candidate belongs
to the the gene cluster thought to contain one or more genes necessary
for a particular resistance specificity. This will be an important initial tool
for identification of gene families involved in resistance in complex genomes
containing many R gene families.
Lagudah ES, Moullet O, Appels R: Map-based cloning of a
gene sequence encoding a nucleotide-binding domain and a
leucine-rich region at the Cre3 nematode resistance locus of
wheat. Genome 1997, 40:650-665.
The first indication that a gene of the NBS-LRR class can encode resistance
to plant parasitic nematodes.
26.
•
27.
Parker JE, Holub EB, Frost LN, Falk A, Gunn ND, Daniels
MJ: Characterization of eds1, a mutation in Arabidopsis
suppressing resistance to Peronospora parasitica specified
by several different RPP genes. Plant Cell 1996, 8:2033-2046.
28.
•
Century KS, Shapiro AD, Repetti PP, Dahlbeck D, Holub E,
Staskawicz BJ: NDR1, a pathogen-induced component required
for Arabidopsis disease resistance. Science 1997, 278:19631965.
This paper demonstrates the power of mutation to identify genes necessary
for resistance and the power of map-based cloning in Arabidopsis. The NDR
protein has no close homologue in the present databases and is predicted
to be a membrane spanning protein. Mutations in NDR1 cause loss of action
of several different R genes.
Van der Biezen EA, Jones JDG: The NB-ARC domain: a novel
signalling motif shared by plant resistance gene products and
regulators of cell death in animals. Curr Biol 1998, 8:R226R227.
This paper draws attention to the extremely strong amino acid sequence
similarity between the nucleotide binding site (NBS) regions of NBS-LRR
(leucine-rich repeat) resistance proteins and CED-4 and Apaf-1, the activators of apoptotic proteases, and provide an interesting model for resistance
protein function whereby NBS-LRR proteins are members of an inactive
cell death-controlling protein complex (apoptosome), possibly including a
capase and Bcl-2 homologue, whose activation is triggered by specific (avr
encoded) pathogen signals. This model lights the fuse of an idea, and time
will tell whether it sets off a bang or a whimper.
39.
••
Parniske M, Hammond-Kosack KE, Golstein C, Thomas CM,
Jones DA, Harrison K, Wulff BBH, Jones JDG: Novel resistance
specificities result from sequence exchange between tandemly
repeated genes at the Cf-4/9 locus. Cell 1997, 91:821-832.
This paper provides the complete molecular description of a complex disease resistance locus in three different genotypes and provides a multicomponent comparison of gene and protein sequences for the elucidation of
possible evolutionary processes and the basis of gene-for-gene specificity.
It also uncovers the hitherto unknown presence within the locus of several
additional genes that express Cladosporium resistance with a different developmental program and specificity.
40.
•
Song W-Y, Pi L-Y, Wang G-L, Gardner J, Holsten T, Ronald PC:
Evolution of the rice Xa21 disease resistance gene family.
Plant Cell 1997, 9:1279-1287.
This paper provided the first insight into a complex R gene locus and indicates that many genes at such loci are pseudogenes inactivated by transposable elements.
41.
Bevan M, Bancroft I, Bent E, Love K, Goodman H, Dean C,
Bergkamp R, Dirkse W, van Staveren M, Stiekema W et al.:
Analysis of 1.9 Mb of contiguous sequence from chromosome
4 of Arabidopsis thaliana. Nature 1998, 391:485-488.
42.
Lemaitre B, Reichhart J-M, Hoffmann JA: Drosophila host
defense: differential induction of antimicrobial peptide genes
after infection by various classes of microorganisms. Proc Natl
Acad Sci USA 1997, 94:14614-14619.
43.
•
Thomas CM, Jones DA, Parniske M, Harrison K, Balint-Kurti P,
Hatzixanthis K, Jones JDG: Characterization of the tomato
Cf-4 gene for resistance to Cladosporium fulvum identifies
sequences that determine recognitional specificity in Cf-4 and
Cf-9. Plant Cell 1997, 9:2209-2224.
29.
•
Structure and function of proteins controlling strain-specific pathogen resistance in plants Ellis and Jones
The comparison of two resistance genes, Cf-4 and Cf-9, for Cladosporium
resistance provides evidence about the regions in Cf proteins that control
specificity of pathogen race recognition.
44.
•
Ellis J, Lawrence G, Ayliffe M, Anderson P, Collins N, Finnegan
J, Frost D, Luck J, Pryor T: Advances in the molecular genetic
analysis of the flax–flax rust interaction. Annu Rev Phytopathol
1997, 35:271-291.
An extensive review of recent activity in the analysis of the flax–flax rust
interaction, which was the host–pathogen system that served as the basis
for Flor’s gene-for-gene hypothesis, and a description of the processes used
for isolating the L6 and M rust resistance genes.
45.
•
Zhou J, Tang X, Martin GB: The Pto kinase conferring resistance
to tomato bacterial speck disease interacts with proteins that
bind a cis-element of pathogenesis-related proteins. EMBO J
1997, 16:3207-3218.
293
The first description of a potential molecular link between a disease resistance receptor and expression of genes involved in defence responses.
46.
•
Buschges R, Hollricher K, Panstruga R, Simons G, Wolter M,
Frijters A, van Daelen R, van der Lee T, Diergaarde P, Groenendijk
J, Topsch S et al.: The barley Mlo gene: a novel control element
of plant pathogen resistance. Cell 1997, 88:695-705.
While the scope of our review was restricted to gene-for-gene resistance,
special attention is also drawn to this recent paper. Recessive mutants of the
Mlo gene are used extensively, especially in Europe, to protect barley from
the fungal disease, mildew. The Mlo gene is unusual in that, in contrast to
gene-for-gene resistance which is usually effective against some but not all
strains of a pathogen species, no barley mildew strains are known in nature
that overcome this resistance. It encodes a novel protein with at least six
predicted membrane spanning helices and none of the structural signatures
of R proteins discussed in our review. The identification of isologues in rice
and Arabidopsis raises the possibility that this form of resistance can be
extended to other plant species.
Structure and function of proteins controlling strain-specific
pathogen resistance in plants
Jeff Ellis∗ and David Jones†
Recently recognised structural and amino acid sequence
similarities between plant disease resistance (R) proteins
and animal proteins such as Apaf-1 and CED-4 are providing
conceptual models for resistance protein function. Data from
extensive DNA sequencing of resistance gene families are
indicating that the leucine-rich repeat motif is an important
determinant of gene-for-gene specificity and that intergenic
DNA sequence exchange is a major contributor to R gene
diversity.
Addresses
∗CSIRO Plant Industry, GPO Box 1600, Canberra ACT 2601,
Australia; e-mail: ellisj@pi.csiro.au
†Research School of Biological Sciences, Australian National
University, PO Box 475, Canberra ACT 2601, Australia; e-mail:
jones@rsbs.anu.edu.au
Current Opinion in Plant Biology 1998, 1:288–293
http://biomednet.com/elecref/1369526600100288
Current Biology Ltd ISSN 1369-5266
Abbreviations
avr
avirulence
IL-1
interleukin-1
LRR
leucine-rich repeat
NBS
nucleotide binding site
PK
protein kinase
R
resistance
TM
transmembrane domain
TIR
Toll and IL-1 receptor
Introduction
Highly polymorphic plant genes (R genes) that control
specific disease resistance [1•], encode proteins in several
classes, some of which bear the hallmarks of innate
immunity and cell death proteins in animals. These
proteins function in surveillance systems for pathogens,
probably detecting pathogen-encoded avirulence gene
products which in other contexts may function as virulence
factors (see [2••] for an excellent example).
Recent reviews (e.g. [1•]) have extensively covered the
comparisons and classification of predicted plant disease
resistance gene products (R proteins) which incorporate
several common structural themes: nucleotide binding
sites (NBSs), leucine-rich repeats (LRRs), transmembrane
domains (TMs) and serine/threonine protein kinases
(PKs). These are combined in several arrangements with
the following signatures, NBS-LRR, LRR-TM-PK, LRRTM and PK. An additional and novel class containing the
Hs1pro-1 nematode resistance protein is discussed in this
review. The largest number of characterised R proteins
are in the NBS-LRR class and so far, proteins in this
class have no other known functions apart from disease
resistance. Similarities between the NBS domain of these
proteins and animal proteins regulating apoptosis (detailed
below), however, suggest that researchers be mindful of
the possibility that some NBS-LRR proteins may function
in plant developmental processes involving programmed
cell death. One example of a ‘multiskilled’ family of
proteins is the LRR-TM-PK class. Although Xa21 is the
only resistance protein in this class, several plant protein
‘relatives’ involved in developmental control and hormone
perception have now been identified, suggesting that Xa21
may have been ‘recruited’ for pathogen detection.
Hs1pro-1: an unusual resistance gene
The predicted protein encoded by the recently cloned
Hs1pro-1 gene for nematode resistance in sugar beet was
reported to have an LRR-TM signature [3], but our
analysis indicates that it does not appear to fit this or
any other of the existing R protein structural signatures.
For example, database searches show no homology to any
previously analysed R gene or LRR protein. Additionally,
the proposed signal peptide and TMs of Hs1pro-1 are
very short and contain a number of charged or polar
residues inconsistent with such roles. Furthermore, the
proposed LRR domain lacks the features of any LRR
consensus that has been described to date, not only
with respect to the spacing of the leucines, but also
regarding the absence of distinctive non-leucine residues.
An Arabidopsis homologue (GenBank accession G2088653)
has been described that was predicted to have a more
extensive amino-terminal domain than Hs1pro-1, but this
shows no better similarity to the LRR-TM signature.
Hs1pro-1 seems likely, therefore, to represent the first
member of an entirely new class of R genes encoding a
novel cytoplasmic proteins.
Xa21: relatives in different professions
The Xa21 gene from rice confers resistance to Xanthomonas
oryzae pv. oryzae (Xoo) and encodes a protein with the
LRR-TM-PK signature in which the LRR is predicted to
be extracellular [4]. So far, Xa21 is the only R protein in
this class. PCR-based methods could provide the means
to clone more R genes in this class, however, this is
clearly not a direct route now that several other plant
genes have been cloned which encode LRR-TM-PK
proteins apparently not involved in pathogen resistance.
These include developmental genes like ERECTA [5]
and CLAVATA1 [6] of Arabidopsis and SERK [7] of carrot,
and the gene encoding a putative brassinosteroid receptor
(BRI) [8] of Arabidopsis. Thus, this class of protein fulfils
several roles in plants. The LRR domain might detect
extracellular ligands of various types, including potentially
Structure and function of proteins controlling strain-specific pathogen resistance in plants Ellis and Jones
the product of the avrXa21 avirulence gene of Xoo.
The involvement of the LRR region of this class in
ligand recognition, however, has not been experimentally
demonstrated and so it is possible that the PK domain of
Xa21, like that of the tomato bacterial resistance protein
Pto which contains only the PK domain [9,10], detects the
corresponding Avr protein.
Xa1, a second rice gene for resistance to Xoo strains
carrying avirulence gene avrXa1, has recently been cloned
and in contrast to Xa21, found to encode a NBS-LRR
protein [11•]. Thus, two unrelated classes of R protein
are used in rice to perceive the same pathogen species
(but different avr genes!). The NBS-LRR proteins
are predicted to be intracellular, whereas the LRR
domain of Xa21 is predicted to be extracellular [12•].
The LRR domains of Xa1 and Xa21, assumed to be
involved in avr ligand binding, are therefore in different
subcellular locations. The cloning and comparison of the
corresponding avr genes, avrXa1 and avrXa2, from Xoo is
keenly anticipated to determine whether the nature and
delivery of the avr ligands reflects these locations.
NBS-LRR resistance proteins: strength in
numbers
The NBS-LRR class is by far the largest group of
resistance proteins. Two subgroups within the NBS-LRR
class have been recognised by the presence or absence
of an amino-terminal region (TIR domain) with amino
acid sequence similarity and predicted structural similarity
[13•,14,15] to the cytoplasmic signalling domains of
the Toll and interleukin-1 (IL-1) receptor. The first
subgroup (TIR-NBS-LRR) includes N (tobacco mosaic
virus resistance, [1•]), L6 (flax rust resistance [1•]), M
(flax rust resistance [16•]) and RPP5 (downy mildew
resistance [13•]). Furthermore, the involvement of plant
and animal TIR proteins in defence processes [15–19]
indicates that they may have their origins in a very ancient
defence mechanism. Recent advances in understanding
the role of Toll and IL-1R in defence processes provide
additional clues about the role of the plant TIR domain.
In Toll/IL-1R signalling, the cytoplasmic TIR domains
are involved in the activation of the PKs Pelle/IRAK
and IRAK-2 via the protein intermediaries Tube/IL-1AcP
and MyD88 [20–23]. Interestingly, MyD88 has an adaptor
protein with an amino-terminal domain similar to those of
IRAK and IRAK-2 and a carboxy-terminal TIR domain
similar to those of IL-1R and IL-1AcP. Heterodimerisation
via the TIR domains on one hand and the amino terminal
domains on the other, might enable MyD88 to act as an
adaptor linking the upstream and downstream components
of the signal transduction process in IL-1R signalling
[21–23]. TIR domains, however, have yet to be detected
among any plant proteins other than the TIR-NBS-LRR
class.
The second subgroup, which lacks the TIR region,
includes the bacterial resistance proteins RPS2, RPM1
289
[1•], Xa1 [11•], Prf [24], the fungal resistance protein I2
[25•] and the possible nematode resistance protein Cre3
[26•]. Of this subgroup, RPS2, RPM1 and Prf are predicted
to contain an amino-terminal leucine zipper (LZ), a motif
frequently involved in protein dimerization. Whether this
motif is functional in dimerisation of R proteins has not
yet been reported and no homologous animal system
with extended similarity in the LZ domain has emerged
upon which to model the function of this domain. The
interaction between this domain and the LZ domain of a
downstream signalling component in a pathway distinct to
that used by the TIR-NBS-LRR subclass seems plausible,
however. Recent genetic evidence indicates that proteins
in these two classes signal through different pathways.
In Arabidopsis, proteins in the TIR class signal via a
pathway that includes EDS1 ([27]; JE Parker, personal
communication) and proteins in the LZ class signal
through a pathway that includes the recently cloned NDR1
gene ([28•]; BJ Staskawicz, personal communication).
Both NDR1 and EDS1 were identified by mutation
screens for loss of disease resistance [27,28•]. There is
no apparent correlation between pathogen type (virus,
fungus, bacterium etc.) and the NBS-LRR subclass used
by plants to detect these pathogens.
NBS-LRRs: the nucleotide binding domain,
an apoptosis connection and a model for
function
Database searches have consistently failed to identify NBS-LRR organisation in bacteria, yeast or animal
genomes. Recently, however, clear and extensive amino
acid sequence similarity in the NBS domain, including
motifs that were previously thought to be common only to
plant NBS-LRR proteins, has been detected in nematode
CED-4 and mammalian Apaf-1 proteins — activators of
the apoptotic proteases CED-3 and caspase-9 respectively
[29•,30••]. One common, but not necessarily universal, feature of NBS-LRR function is the occurrence
of hypersensitive cell death at infection sites during
resistance reactions. The similarity between this response
and animal apoptosis has often been remarked upon, so
this structural similarity between the NBS-LRR proteins
and CED-4 and Apaf-1 is intriguing. Experimental
evidence for nucleotide binding at the NBS site has been
obtained for CED-4 [30••] and for the RPS2 resistance
protein (A Bent, personal communication), suggesting
a functional similarity. CED-4 and Apaf-1 appear to
act as adaptor molecules with a central NBS domain
and an amino-terminal effector domain [30••,31]. The
carboxy-terminal receptor domain of Apaf-1 is composed
of repeating amino acid motifs, designated WD-40 repeats,
involved in protein–protein interactions (analogous to
the LRR domain) [31]. Interestingly, both CED-4 and
Apaf-1 appear to activate their target proteases (CED-3
and caspase-9 respectively) by heterodimerisation of
homologous amino-terminal domains present in both the
activators and the proteases [30••,32]. This is reminiscent
of the interaction between homologous domains of MyD88
290
Plant–microbe interactions
and other components of the IL-1R system discussed
above and encourages a search for plant proteins that may
interact through homology with the TIR or LZ domains
of resistance proteins.
Many NBS-LRR plant genes have been identified through
plant genome sequencing projects [33] and by PCR
using redundant primers based on NBS motifs [34–37].
Programmed cell death is used in plant developmental
processes and the question arises whether any of these
newly identified NBS-LRRs lacking ascribed resistance
function may have a role in development rather than
resistance.
Resistance genes at complex loci
Genetic mapping of resistance gene specificities has
indicated that they frequently cluster at complex loci.
Sequence data now show that such loci represent all
classes of R genes except Hs1pro-1, and contain tandem
arrays of closely related genes [25•,38,39••,40•]. The
tomato Cf-4/9 locus (LRR-TM class) from two lines (Cf4
and Cf9) and the tomato Pto locus (PK class) contain
multiple genes, most of which appear to be functional
[38], while the rice Xa21 locus (LRR-TM-PK class) [40•]
and the Arabidopsis RPP5 locus (TIR-NBS-LRR class)
from ecotype Col-O [41] contain a high proportion of
pseudogenes, with several carrying transposons, deletions
or frame shifts. These arrays of paralogous genes may
provide a means of maintaining favourable haplotypes
with multiple specificities or may act as reservoirs of
sequence diversity for generating new specificities by
intergenic sequence exchange. In contrast, members of the
LRR-TM-PK class mentioned above as developmental
regulators or hormone receptors occur as single genes at
simple loci. The latter proteins are likely to be focused
on single ligands that are evolutionarily stable in contrast
to rapidly changing pathogen ligands. Simple R gene loci
also exist and in at least one case, the L rust resistance
locus in flax, diversity is provided by a multiply allelic
series. In a number of cases, however, such as RPS2
[1•], RPM1 [1•], and Xa1 [11•], the R genes exist as
single genes at simple loci with only a single recognitional
specificity. Furthermore, complexity at a particular locus
can be variable; for example, only a single gene occurs
at the Cf-4/9 locus in the susceptible Cf0 line of tomato
[39••], probably reflecting deletion events resulting from
unequal crossing over at an ancestral complex locus.
Resistance gene specificity
All of the R genes discussed in this review show a high
level of recognitional specificity, that is, they provide resistance against only some strains of a particular pathogen
species. This is principally the result of a high level of
polymorphism among pathogen avirulence genes which
encode the probable ligands of the resistance protein
receptors. This contrasts with our current perception of the
innate immunity systems in Drosophila where specificity is
manifest against common ligands within pathogen classes,
for example, Gram-positive or Gram-negative bacteria or
fungal pathogens [42].
Three systems are currently providing insight into the
molecular basis of specificity in pathogen strain recognition. In the interaction between the tomato Pto and
Pseudomonas syringae AvrPto proteins, domain swap experiments between Pto and another closely related gene, Fen,
at the complex Pto locus and yeast two-hybrid analysis
of the chimeric genes have identified a small region of
Pto involved in the interaction with AvrPto and thus
also involved in the determination of specificity towards
races of P. syringae carrying the avrPto gene [9,10]. In the
second system, also in tomato, 11 homologous genes at the
Cf-4/9 locus for Cladosporium fulvum resistance have been
sequenced [39••]. Comparison of the predicted amino
acid sequences shows conservation in the carboxy-terminal
halves of the proteins, which include about a third of the
LRRs; an extreme example being complete identity in
the carboxy-terminal halves of the Cf-4 and Cf-9 proteins
[43•]. This implies that the specificity of recognition
of avirulence ligands is determined by the LRRs of
the variable amino-terminal regions. These comparisons
also show that variation within the amino-terminal LRR
region occurs predominantly in regions predicted to form
a solvent-exposed parallel sheet and thought to provide a
platform for the presentation of nonconserved residues for
specific interaction with protein ligands [12•].
Analysis of the nucleotide sequence of these 11 homologues revealed variation originating from mutation, segmental exchange between adjacent homologues within
tandem arrays (either by repeated rounds of unequal
exchange or by gene conversion) and duplication or
deletion of complete LRR units; for example, Cf-4 differs
from Cf-9 by a precise deletion of two complete LRRs
[43•]. The predicted parallel β-sheet arrangement of LRRs
means that a given amino acid has both a horizontal
context — the neighbouring amino acids within its own
LRR unit, and a vertical context — amino acids in a similar
position in the two flanking LRRs. Segmental exchange,
although it may have had a limited role in producing
novel combinations in the horizontal context, would seem
to have had a more important role in producing novel
combinations of amino acids in the vertical context.
Deletion and duplication of LRRs would have the same
effect.
In the third system, the predicted protein sequences of
13 active alleles of the flax L gene (TIR-NBS-LRR)
conferring rust resistance [44•] are over 90% identical
but show variation over the entire length of the protein.
The greatest sequence variation is observed in the LRR
region. The same three sources of variation acting on the
Cf genes also appear to operate for LRR domains of the
L alleles. Selection seems to be acting in a similar way
to favour diversification in the potential strand regions
and conservation in the nonstrand regions of the LRR
Structure and function of proteins controlling strain-specific pathogen resistance in plants Ellis and Jones
domain. Sequence comparisons and interallelic domain
swap experiments, however, also indicate that the aminoterminal TIR domain makes important contributions to
allelic specificity in addition to the LRR domain (J Ellis et
al., unpublished data).
4.
Song W-Y, Wang G-L, Chen L-L, Kim H-S, Pi L-Y, Holsten T,
Gardner J, Wang B, Zhai W-X, Zhu L-H et al.: A receptor kinaselike protein encoded by the rice disease resistance gene,
Xa21. Science 1995, 270:1804-1806.
5.
Torii KU, Mitsukawa N, Oosumi T, Matsuura Y, Yokoyama R,
Whittier RF, Komeda Y: The Arabidopsis ERECTA gene encodes
a putative receptor protein kinase with extracellular leucinerich repeats. Plant Cell 1996, 8:735-746.
6.
Clark SE, Williams RW, Meyerowitz EM: The CLAVATA1 gene
encodes a putative receptor kinase that controls shoot and
floral meristem size in Arabidopsis. Cell 1997, 89:575-585.
7.
Schmidt EDL, Guzzo F, Toonen MAJ, de Vries SC: A leucinerich repeat containing receptor-like kinase marks somatic
plant cells competent to form embryos. Development 1997,
124:2049-2062.
8.
Li J, Chory J: A putative leucine-rich repeat receptor kinase
involved in brassinosteroid signal transduction. Cell 1997,
90:929-938.
9.
Scofield SR, Tobias CM, Rathjen JP, Chang JH, Lavelle DT,
Michelmore RW, Staskawicz BJ: Molecular basis of gene-forgene specificity in bacterial speck disease of tomato. Science
1996, 274:2063-2065.
10.
Tang XY, Frederick RD, Zhou JM, Halterman DA, Jia YL, Martin
GB: Initiation of plant disease resistance by physical
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Conclusions
The number of cloned R genes is rapidly increasing and genetic and molecular studies have identified
several downstream signalling components in resistance
[27,28•,45•]. One example of a strain-nonspecific resistance gene, mlo, has been cloned [46•] and analysis and
engineering of the homologues in other plant species may
lead to further examples of ‘broad spectrum resistance’.
Basic information concerning how these genes function
is appearing more slowly, but genomic and comparative
studies are providing leads. In only one example (Avr Pto
and Pto [9,10]) has evidence of direct interaction between
a resistance and avirulence protein been reported, in
spite of the fact that several other cloned bacterial
and fungal avirulence genes corresponding to cloned
resistance genes are available. The possibility remains
that these interactions will involve one or more additional
host proteins as in the animal apoptosome complex
which involves Apaf-1, Bcl-2 and Caspase 3 [29•]. Many
avirulence genes corresponding to cloned resistance genes
are yet to be cloned and no X-ray crystallographic analysis
of R proteins has been reported. Thus several critical areas
of ignorance are ripe for illumination in the near future.
References and recommended reading
Papers of particular interest, published within the annual period of review,
have been highlighted as:
• of special interest
•• of outstanding interest
1.
Hammond-Kosack KE, Jones JDG: Plant disease resistance
•
genes. Annu Rev Plant Physiol Plant Mol Biol 1997, 48:575-607.
An extensive review of cloned plant disease resistance genes and comparison of their products.
2.
••
Bogdanove AJ, Kim JF, Wei Z, Kolchinsky P, Charkowski AO,
Conlin AK, Collmer A, Beer SV: Homology and functional
similarity of an hrp-linked pathogenicity locus, dspEF,
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USA 1998, 95:1325-1330.
The function of pathogen avirulence genes has been enigmatic. Several
examples among plant bacterial pathogens have indicated that avirulence
gene mutants have decreased virulence. This paper describes two dspEF
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for virulence. When transferred and expressed in Pseudomonas syringae,
however, they function as avirulence genes and induce defence responses
in specific resistant lines of soybean. Avirulence genes with high sequence
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Cai D, Kleine M, Kifle S, Harloff H-J, Sandal NN, Marcker KA,
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The map-based cloning of a second blight resistance gene in rice is described and the amino acid sequence predicted. The predicted product contains six near perfect 93 amino acid repeats in the LRR region and Xa1 expression is induced by infection and wounding. Whether any other R genes
are induced has not been addressed in any detail in previous publications.
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•
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An extensive review of plant LRR proteins and discussion of features that
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Arabidopsis downy mildew resistance gene RPP5 shares
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Plant Cell 1997, 9:879-894.
Like [16•] this paper describes a deletion event involving repeated sequence
elements in the leucine-rich repeat region and indicates that these events
may play a role in the evolution of the genes.
14.
Baker B, Zambryski P, Staskawicz B, Dinesh-Kumar SP: Signaling
in plant-microbe interactions. Science 1997, 276:726-733.
15.
Rock FL, Hardiman G, Timans JC, Kastelein RA, Bazan JF: A
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16.
•
Anderson PA, Lawrence GJ, Morrish BC, Ayliffe MA, Finnegan
EJ, Ellis JG: Inactivation of the flax rust resistance gene M
associated with the loss of a repeated unit within the leucinerich repeat coding region. Plant Cell 1997, 9:641-651.
A description of the TIR-NBS-LRR (Toll and Interleukin 1 receptor-nuclear
binding site-leucine rich repeat) flax rust resistance gene M and of mutants
that arise by intragenic events involving two direct repeats in the LRR. It compares M with L6, two highly related products with different rust resistance
specificity, the former being encoded by a complex tandem array of genes
and the latter by a single gene with multiple alleles at a simple locus.
17.
Lemaitre B, Nicolas E, Michaut L, Reichhart J-M, Hoffmann JA:
The dorsoventral regulatory gene cassette spätzle/Toll/cactus
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Williams MJ, Rodriguez A, Kimbrell DA, Eldon ED: The 18-wheeler
mutation reveals complex antibacterial gene regulation in
Drosophila defense. EMBO J 1997, 16:6120-6130.
19.
Medzhitov R, Preston-Hurlburt P, Janeway CA: A human
homologue of the Drosophila Toll protein signals activation of
adaptive immunity. Nature 1997, 338:394-397.
20.
Yang J, Steward R: A multimeric complex and the nuclear
targeting of the Drosophila rel protein dorsal. Proc Natl Acad
Sci USA 1997, 94:14524-14529.
21.
Muzio M, Ni J, Feng P, Dixit VM: IRAK (Pelle) family member
IRAK-2 and MyD88 as proximal mediators of IL-1 signaling.
Science 1997, 278:1612-1615.
22.
30.
••
Chinnaiyan AM, Chaudhary D, O’Rourke K, Koonin EV, Dixit VM:
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••
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The first description of a potential molecular link between a disease resistance receptor and expression of genes involved in defence responses.
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•
Buschges R, Hollricher K, Panstruga R, Simons G, Wolter M,
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special attention is also drawn to this recent paper. Recessive mutants of the
Mlo gene are used extensively, especially in Europe, to protect barley from
the fungal disease, mildew. The Mlo gene is unusual in that, in contrast to
gene-for-gene resistance which is usually effective against some but not all
strains of a pathogen species, no barley mildew strains are known in nature
that overcome this resistance. It encodes a novel protein with at least six
predicted membrane spanning helices and none of the structural signatures
of R proteins discussed in our review. The identification of isologues in rice
and Arabidopsis raises the possibility that this form of resistance can be
extended to other plant species.