The panels in the top row show schematic representations of the different types of binding sites in a fab fragment of an antibody: first panel, pocket; second panel, groove; third panel, extended surface; and fourth panel, protruding surface. Below are examples of each type. Panel a: the top image shows the molecular surface of the interaction of a small hapten with the complementarity-determining regions (cDRs) of a fab fragment as viewed looking into the antigen-binding site. The ferrocene hapten, shown in red, is bound into the antigen-binding pocket (yellow). in the bottom image (and in those of panels b, c, and d), the molecule has been rotated by about 90° to give a side-on view of the binding site. Panel b: in a complex of an antibody with a peptide from the human immunodeficiency virus (hiV), the peptide (red) binds along a groove (yellow) formed between the heavy-chain and light-chain V domains. Panel c: shown is a complex between hen egg-white lysozyme and the fab fragment of its corresponding antibody (hyhel5). The surface on the antibody that comes into contact with the lysozyme is colored yellow. All six cDRs of the antigen-binding site are involved in the binding. Panel d: an antibody molecule against the hiV gp120 antigen has an elongated cDR3 loop (arrow) that protrudes into a recess on the side of the antigen. The structure of the complex between this antibody and gp120 has been solved, and in this case only the heavy chain interacts with gp120. Structures courtesy of R.L. Stanfield and i.A. Wilson.
Fig. 4.8 Antigens can bind in pockets, or grooves, or on extended surfaces in the binding sites of antibodies.
peptide, generally binds in a pocket or groove lying between the heavy-chain and light-chain V domains (Fig. 4.8a and b). Some antigens, such as proteins, can be the same size as, or larger than, the antibody itself. In these cases, the interface between antigen and antibody is often an extended surface that involves all the CDRs and, in some cases, part of the framework region as well (see Fig. 4.8c). This surface need not be concave but can be flat, undulating, or even convex. In some cases, antibody molecules with elongated CDR3 loops can protrude a ‘finger’ into recesses in the surface of the antigen, as shown in Fig. 4.8d, where an antibody binding to the HIV gp120 antigen projects a long loop into its target.
4-8 Antibodies bind to conformational shapes on the surfaces of antigens using a variety of noncovalent forces.