Although all the information required for the folding of a protein chain is contained in its amino
22 Although all the information required for the folding of a protein chain is contained in its amino
acid sequence, we have not yet learned how to "read" this information so as to predict the detailed three-dimensional structure of a protein whose sequence is known. Consequently, the folded conformation can be determined only by an elaborate x-ray diffraction analysis performed on crystals of the protein or, if the protein is very small, by nuclear magnetic resonance techniques (see Chapter 4). So far, more than 100 types of protein folds have been discovered by this technique. Each protein has a specific conformation so intricate and irregular that it would require a chapter to describe it in full three-dimensional detail.
When the three-dimensional structures of different protein molecules are compared, it becomes clear that, although the overall conformation of each protein is unique, several structural patterns recur repeatedly in parts of these macromolecules. Two patterns are particularly common because they result from regular hydrogen-bonding interactions between the peptide bonds themselves rather than between the side chains of particular amino acids. Both patterns were correctly predicted in 1951 from model-building studies based on the different x-ray diffraction patterns of silk and hair. The two regular patterns discovered are now known as the β sheet, which occurs in the protein fibroin, found in silk, and the α helix, which occurs in the protein α - keratin, found in skin and its appendages, such as hair, nails, and feathers.
The core of most (but not all) globular proteins contains extensive regions of β sheet. In the example illustrated in Figure 3-29, which shows part of an antibody molecule, an antiparallel β sheet is formed when an extended polypeptide chain folds back and forth upon itself, with each section of the chain running in the direction opposite to that of its immediate neighbors. This gives
a very rigid structure held together by hydrogen bonds that connect the peptide bonds in neighboring chains. The antiparallel β sheet and the closely related parallel β sheet (which is formed by regions of polypeptide chain that run in the same direction) frequently serve as the framework around which globular proteins are constructed.
An α helix is generated when a single polypeptide chain turns regularly about itself to make a rigid cylinder in which each peptide bond is regularly hydrogen-bonded to other peptide bonds nearby in the chain. Many globular proteins contain short regions of such α helices ( Figure 3-30), and those portions of a transmembrane protein that cross the lipid bilayer are usually α helices because of the constraints imposed by the hydrophobic lipid environment (discussed in Chapter 10).
In aqueous environments an isolated α helix is usually not stable on its own. Two identical α helices that have a repeating arrangement of nonpolar side chains, however, will twist around each other gradually to form a particularly stable structure known as a coiled-coil (see p. 125). Long rodlike coiled-coils are found in many fibrous proteins, such as the intracellular α -keratin fibers that reinforce skin and its appendages.
Space-filling representations of an α helix and a β sheet from actual proteins are shown with and without their side chains in Figure 3-31.