A COMPARISON OF THE FOLDING KINETICS AND THERMODYNAMICS OF 2 HOMOLOGOUS FIBRONECTIN TYPE-III MODULES

The homologous ninth and tenth type III modules of human fibronectin s hare identical topologies and nearly identical core structures. Despit e these structural similarities, the refolding characteristics of the two modules, which have a sequence identity of less than 30 %, are ver y different; in the absence of denaturant the ninth module folds sever al hundred times more slowly than the tenth and, although both modules contain numerous proline residues, only the ninth exhibits a slow, pr oline isomerization-limited folding phase. The different folding kinet ics of the two modules coincide with a large difference in their therm odynamic stability, with the folding free energy of the tenth being ap proximately five fold greater than that of the ninth. This may be the reason why the ninth module, unlike the rapidly folding tenth module, is apparently unable to overcome characteristics of the fibronectin ty pe III modules that can slow the folding process. The non-proline-limi ted folding kinetics are, however, very similar for the two modules wh en compared under conditions where their overall stabilities are simil ar. The significance of this finding is discussed in terms of possible determinants of the kinetics of protein folding. (C) 1997 Academic Pr ess Limited.