ANALYSIS OF ANTIGENIC SURFACES OF PROTEINS

The processes underlying molecular evolution have proved difficult to understand due to the complexity and obscurity of the selective pressu res at work. The strong selective pressure to optimize antigen recogni tion means that antibody paratopes are more favorable systems than mos t in which to investigate these processes, as are viral epitopes, whic h evolve under an inverse pressure, rapidly changing to avoid recognit ion. Because recognition is a property of the surfaces of these molecu les we expect that their evolutionary development may be read in the c hanges in the 3-dimensional array of chemical groups displayed on thei r surface. We have analyzed the bulk properties of these surfaces and find that there are significant differences in exposed amino acid pref erences among 1) a control group of immunologically secluded proteins, 2) binding surfaces of immunoglobulins, and 3) the outer surfaces of picornaviruses. Compared to the control group, the immunoglobulin comp lementarity determining regions possess a relative excess of serine re sidues whereas picornaviruses suppress serine but overuse threonine re sidues, suggesting that the differing selective pressure has led to pe rturbations in the population of amino acid types on the surface of th ese proteins. Although these changes may be rationalized in terms of t he structure and chemistry of the different side chains, we suggest th at there may be a further, genetic component behind the observations: point mutations in the respective codons for serine and threonine lead to markedly different forms of structural variability. The high rate of reselection observed for these residues is in line with this second mechanism.