Convergent solutions to binding at a protein-protein interface

The hinge region on the Fe fragment of human immunoglobulin G interacts wit h at least four different natural protein scaffolds that bind at a common s ite between the C-H2 and C-H3 domains. This "consensus" site was also domin ant for binding of random peptides selected in vitro for high affinity (dis sociation constant, about 25 nanomolar) by bacteriophage display, Thus, thi s site appears to be preferred owing to its intrinsic physiochemical proper ties, and not for biological function alone. A 2.7 angstrom crystal structu re of a selected 13-amino acid peptide in complex with Fc demonstrated that the peptide adopts a compact structure radically different from that of th e other Fc binding proteins. Nevertheless, the specific Fc binding interact ions of the peptide strongly mimic those of the other proteins. Juxtapositi on of the available Fc-complex crystal structures showed that the convergen t binding surface is highly accessible, adaptive, and hydrophobic and conta ins relatively few sites for polar interactions. These are all properties t hat may promote cross-reactive binding, which is common to protein-protein interactions and especially hormone-receptor complexes.