Front and back views of a space-filling model of the SH2 domain, with evolutionarily conserved amino acids on the protein surface colored yellow, and those more toward the protein interior colored red. (B) The structure of one specific SH2 domain with its bound polypeptide. Here, those amino acids located within 0.4 nm of the bound ligand are colored blue. The two key amino acids of the ligand are yellow, and the others are purple. Note the high degree of correspondence between and (B). (Adapted from O. Lichtarge,
H.R. Bourne and F.E. Cohen, J. Mol. Biol. 257:342–358, 1996. With permission from Elsevier; PDB codes: 1SPR, 1SPS.)
Figure 3–41 Three ways in which two proteins can bind to each other. Only the interacting parts of the two proteins are shown. (A) A rigid surface on one protein can bind to an extended loop of polypeptide chain (a “string”) on a second protein. (B) Two α helices can bind together to form a coiled-coil.
(C) Two complementary rigid surfaces often link two proteins together. Binding interactions can also involve the pairing of β strands (see, for example, Figure 3–18).
hypervariable loops variable domain of light chain (VL) (B) constant domain of light chain (CL) disulfde bond COOH NH2 S S S S SS SSSSSSSSVL CL VH CH1CH1 CH2 CH3 Figure 3–42 an antibody molecule.  A typical antibody molecule is Y-shaped and has two identical binding sites for its antigen, one on each arm of the Y. As explained in Chapter 24, the protein is composed of four polypeptide chains (two identical heavy chains and two identical and smaller light chains) held together by disulfide bonds. Each chain is made
All proteins must bind to particular ligands to carry out their various functions. The antibody family is notable for its capacity for tight, highly selective binding (discussed in detail in Chapter 24).
Antibodies, or immunoglobulins, are proteins produced by the immune system in response to foreign molecules, such as those on the surface of an invading microorganism. Each antibody binds tightly to a particular target molecule, thereby either inactivating the target molecule directly or marking it for destruction. An antibody recognizes its target (called an antigen) with remarkable specificity. Because there are potentially billions of different antigens that humans might encounter, we have to be able to produce billions of different antibodies.
Antibodies are Y-shaped molecules with two identical binding sites that are complementary to a small portion of the surface of the antigen molecule. A detailed examination of the antigen-binding sites of antibodies reveals that they are formed from several loops of polypeptide chain that protrude from the ends of a pair of closely juxtaposed protein domains (Figure 3–42). Different antibodies generate an enormous diversity of antigen-binding sites by changing only the length and amino acid sequence of these loops, without altering the basic protein structure.
Loops of this kind are ideal for grasping other molecules. They allow a large number of chemical groups to surround a ligand so that the protein can link to it with many weak bonds. For this reason, loops often form the ligand-binding sites in proteins.
The Equilibrium Constant Measures Binding Strength
Molecules in the cell encounter each other very frequently because of their continual random thermal movements. Colliding molecules with poorly matching surfaces form few noncovalent bonds with one another, and the two molecules dissociate as rapidly as they come together. At the other extreme, when many noncovalent bonds form between two colliding molecules, the association can persist for a very long time (Figure 3–43). Strong interactions occur in cells whenever a biological function requires that molecules remain associated for a long time—for example, when a group of RNA and protein molecules come together to make a subcellular structure such as a ribosome.