A protein molecule’s amino acid sequence determines its three-dimensional conformation. Noncovalent interactions between different parts of the polypeptide chain stabilize its folded structure. The amino acids with hydrophobic side chains tend to cluster in the interior of the molecule, and local hydrogen-bond interactions between neighboring peptide bonds give rise to α helices and β sheets.
Regions of amino acid sequence known as domains are the modular units from which many proteins are constructed. Such domains generally contain 40–350 amino acids, often folded into a globular shape. Small proteins typically consist of only a single domain, while large proteins are formed from multiple domains linked together by various lengths of polypeptide chain, some of which can be relatively disordered. As proteins have evolved, domains have been modified and combined with other domains to construct large numbers of new proteins.
Proteins are brought together into larger structures by the same noncovalent forces that determine protein folding. Proteins with binding sites for their own surface can assemble into dimers, closed rings, spherical shells, or helical polymers. The amyloid fibril is a long unbranched structure assembled through a repeating aggregate of β sheets. Although some mixtures of proteins and nucleic acids can assemble spontaneously into complex structures in a test tube, not all structures in the cell are capable of spontaneous reassembly after they have been dissociated into their component parts, because many biological assembly processes involve assembly factors that are not present in the final structure.
We have seen that each type of protein consists of a precise sequence of amino acids that allows it to fold up into a particular three-dimensional shape, or conformation. But proteins are not rigid lumps of material. They often have precisely engineered moving parts whose mechanical actions are coupled to chemical events. It is this coupling of chemistry and movement that gives proteins the extraordinary capabilities that underlie the dynamic processes in living cells.
In this section, we explain how proteins bind to other selected molecules and how a protein’s activity depends on such binding. We show that the ability to bind to other molecules enables proteins to act as catalysts, signal receptors, switches, motors, or tiny pumps. The examples we discuss in this chapter by no means exhaust the vast functional repertoire of proteins. You will encounter the specialized functions of many other proteins elsewhere in this book, based on similar principles.
All Proteins Bind to Other Molecules
A protein molecule’s physical interaction with other molecules determines its biological properties. Thus, antibodies attach to viruses or bacteria to mark them for destruction, the enzyme hexokinase binds glucose and ATP so as to catalyze a reaction between them, actin molecules bind to each other to assemble into actin filaments, and so on. Indeed, all proteins stick, or bind, to other molecules. In some cases, this binding is very tight; in others it is weak and short-lived. But the binding always shows great specificity, in the sense that each protein molecule can usually bind just one or a few molecules out of the many thousands of different types it encounters. The substance that is bound by the protein—whether it is an ion, a small molecule, or a macromolecule such as another protein—is referred to as a ligand for that protein (from the Latin word ligare, meaning “to bind”).
The ability of a protein to bind selectively and with high affinity to a ligand depends on the formation of a set of weak noncovalent bonds—hydrogen bonds, electrostatic attractions, and van der Waals attractions—plus favorable hydrophobic interactions (see Panel 2–3, pp. 94–95). Because each individual bond is weak, effective binding occurs only when many of these bonds form simultaneously. Such binding is possible only if the surface contours of the ligand molecule fit very closely to the protein, matching it like a hand in a glove (Figure 3–37).