KINETIC PARTITIONING - POISING SECB TO FAVOR ASSOCIATION WITH A RAPIDLY FOLDING LIGAND

Chaperones are a class of proteins that possess the remarkable ability to selectively bind polypeptides that are in a nonnative state, The s electivity of SecB, a molecular chaperone in Escherichia coli, for its Ligands can be explained in part by a kinetic partitioning between fo lding of the polypeptide and association with SecB. It has clearly bee n established that kinetic partitioning can be poised to favor associa tion with SecB by changing the rate constant for folding of the ligand , We now demonstrate that binding to SecB can be given a kinetic advan tage over the pathway for folding by modulating the properties of the chaperone. By poising SecB to expose a hydrophobic patch, we were able to detect a complex between SecB and maltose-binding protein under co nditions in which rapid folding of the polypeptide otherwise precludes formation of a kinetically stable complex. The data presented here ar e interpreted within the framework of a kinetic partitioning between b inding to SecB and folding of the polypeptide. We propose that exposur e of a hydrophobic patch on SecB increases the surface area for bindin g and thereby increases the rate constant for association. In this way association of SecB with the polypeptide ligand has a kinetic advanta ge over the pathway for folding.