Degenerate interfaces in antigen-antibody complexes

In most of the work dealing with the analysis of protein-protein interfaces , a single X-ray structure is available or selected, and implicitly it is a ssumed that this structure corresponds to the optimal complex for this pair of proteins. However, we have found a degenerate interface in a high-affin ity antibody-antigen complex: the two independent complexes of the camel va riable domain antibody fragment cAb-Lys3 and its antigen hen egg white lyso zyme present in the asymmetric unit of our crystals show a difference in re lative orientation between antibody and antigen, leading to important diffe rences at the protein-protein interface. A third cAb-Lys3-hen lysozyme comp lex in a different crystal form adopts yet another relative orientation. Ou r results show that protein-protein interface characteristics can vary sign ificantly between different specimens of the same high-affinity antibody-pr otein antigen complex. Consideration should be given to this type of observ ation when trying to establish general protein-protein interface characteri stics. (C) 2001 Academic Press.