Figure 3–25 Disulfide bonds. Covalent disulfide bonds form between adjacent cysteine side chains. These cross-linkages can join either two parts of the same polypeptide chain or two different polypeptide chains. Since the energy required to break one covalent bond is much larger than the energy required to break even a whole set of noncovalent bonds (see Table 2–1, p. 45), a disulfide bond can have a major stabilizing effect on a protein (Movie 3.7).
Many protein molecules are either attached to the outside of a cell’s plasma membrane or secreted as part of the extracellular matrix. All such proteins are directly exposed to extracellular conditions. To help maintain their structures, the polypeptide chains in such proteins are often stabilized by covalent cross-linkages. These linkages can either tie together two amino acids in the same protein, or connect different polypeptide chains in a multisubunit protein. Although many other types exist, the most common cross-linkages in proteins are covalent sulfur– sulfur bonds. These disulfide bonds (also called S–S bonds) form as cells prepare newly synthesized proteins for export. As described in Chapter 12, their formation is catalyzed in the endoplasmic reticulum by an enzyme that links together two pairs of –SH groups of cysteine side chains that are adjacent in the folded protein (Figure 3–25). Disulfide bonds do not change the conformation of a protein but instead act as atomic staples to reinforce its most favored conformation. For example, lysozyme—an enzyme in tears that dissolves bacterial cell walls—retains its antibacterial activity for a long time because it is stabilized by such cross-linkages.
Disulfide bonds generally fail to form in the cytosol, where a high concentration of reducing agents converts S–S bonds back to cysteine –SH groups. Apparently, proteins do not require this type of reinforcement in the relatively mild environment inside the cell.
Protein Molecules Often Serve as Subunits for the Assembly of Large Structures
The same principles that enable a protein molecule to associate with itself to form rings or a long filament also operate to generate much larger structures formed from a set of different macromolecules, such as enzyme complexes, ribosomes, viruses, and membranes. These large objects are not made as single, giant, covalently linked molecules. Instead they are formed by the noncovalent assembly of many separately manufactured molecules, which serve as the subunits of the final structure.
The use of smaller subunits to build larger structures has several advantages: 1.
A large structure built from one or a few repeating smaller subunits requires only a small amount of genetic information.
2.
Both assembly and disassembly can be readily controlled reversible processes, because the subunits associate through multiple bonds of relatively low energy.
3.
Errors in the synthesis of the structure can be more easily avoided, since correction mechanisms can operate during the course of assembly to exclude malformed subunits.
Some protein subunits assemble into flat sheets in which the subunits are arranged in hexagonal patterns. Specialized membrane proteins are sometimes arranged this way in lipid bilayers. With a slight change in the geometry of the individual subunits, a hexagonal sheet can be converted into a tube (Figure 3–26) or, with more changes, into a hollow sphere. Protein tubes and spheres that bind specific RNA and DNA molecules in their interior form the coats of viruses.