The importance of conformation and of equilibria in the interaction of globular proteins and their fragments with antibodies.

Abstract

Oligopeptide fragments of globular proteins often inhibit the interaction of antibodies with native protein. Although such fragments appear to possess in aqueous solution an unfolded conformation it is apparent, in those cases where the protein's three-dimensional structure is known, that the antibody-bound fragment possesses a folded conformation mimicking that of the corresponding portion of the whole protein. The probable explanation of this dichotomy is that the fragment has various conformations in equilibrium including a small proportion of molecules whose shape is recognized and stabilized by the antibody. A related situation can exist in the interaction of antibody(ies) with the whole protein. Thus, antibodies against an altered form of the protein can induce the native antigen to adopt the conformation of the altered form. In this case, it appears that localized regions of the protein's surface are flexible, adopting various conformations in equilibrium, one of which is stabilized (selected) by interaction with the appropriate antibody. In both instances interaction with antibody perturbs an equilibrium, leading to the selection of a particular conformation. Such dynamic effects have profound implications on the choice of peptides as synthetic vaccines.