Tentative Sequential Model for the Unfolding and Refolding of Staphylococcal Nuclease at High pH

the folding of a protein appear as highly co-operative processes in both kinetic and thermo-dynamic measurements (Tanford, 1968). Most methods which have been used to date to study these phenomena llow a clear-cut identification of the initial (i.e., native) and final (i.e., denatured) states, but reveal intermediate states in relatively few cases (Roberts and Jardetzky, 1970). To a rough approximation the transition may therefore seem to be a single step between only two states. On the other hand, detailed examination of the crystal structure of several proteins leads to the conclusion that both the folding and unfolding are more likely to proceed as a relatively well-defined sequence of events. That is, certain parts of the