Reversible Binding of a Protein to a Ligand: Oxygen-Binding Proteins: -Antibodies Bind Tightly and Specifically to Antigen
The binding specificity of an antibody is determined by the amino acid residues in the variable domains of its heavy and light chains. Many residues in these domains are variable, but not equally so. Some, particularly those lining the antigen-binding site, are hypervariable— especially likely to differ. Specificity is conferred by chemical complementarity between the antigen and its specific binding site, in terms of shape and the location of charged, nonpolar, and hydrogen-bonding groups. For example, a binding site with a negatively charged group may bind an antigen with a positive charge in the com plementary position. In many instances, complementarity is achieved interactively as the structures of antigen and binding site are influenced by each other during the approach of the ligand. Conformational changes in the antibody and/or the antigen then occur that allow the complementary groups to interact fully. This is an ex ample of induced fit (Fig. 5–27).
FIGURE 5–27 Induced fit in the binding of an antigen to IgG. The molecule, shown in surface contour, is the Fab fragment of an IgG. The antigen bound by this IgG is a small peptide derived from HIV. Two residues from the heavy chain (blue) and one from the light chain (pink) are colored to provide visual points of reference. (a) View of the Fab fragment, looking down on the antigen-binding site (PDB ID1GGC). (b)The same view, but here the Fab fragment is in the “bound” conformation (PDB ID 1GGI); the antigen has been omitted from the image to provide an unobstructed view of the altered binding site. Note how the binding cavity has enlarged and several groups have shifted position. (c) The same view as in (b), but with the antigen in the binding site, pictured as a red stick structure.
A typical antibody-antigen interaction is quite strong, characterized by Kd values as low as 10-10 M (re call that a lower Kd corresponds to a stronger binding interaction). The Kd reflects the energy derived from the various ionic, hydrogen-bonding, hydrophobic, and van der Waals interactions that stabilize the binding. The binding energy required to produce a Kd of 10-10 M is about 65 kJ/mol. The complex of a peptide derived from HIV (a model antigen) and an Fab molecule, shown in Figure 5–27, il lustrates some of these properties. The changes in structure observed on antigen binding are particularly striking in this example.
