TOPOLOGY, SEQUENCE EVOLUTION AND FOLDING DYNAMICS OF AN IMMUNOGLOBULIN DOMAIN

The pH-dependence of hydrogen-exchange, in native conditions, is used to probe the formation of secondary structure in the folding of an imm unoglobulin domain (CD2.d1). The intermediate and transition states in the reaction are insensitive to pH, a simplification that allows us t o equate structure formation and folding kinetics. The crucial residue s in the folding reaction are grouped in the B, C, E and F strands whi ch constitute a 'crossover' nucleus in the beta-sandwich. These residu es show the highest sequence conservation within the family of folds t o which this domain belongs and are located in a unit of structure tha t is the most consistent topological feature of the immunoglobulin fam ily.