Chaperone-percolator model: a possible molecular mechanism of Anfinsen-cage-type chaperones.

Although we have a rather elaborate "working-cycle" for the 60 kDa molecular chaperones, which possess a cavity, and are called Anfinsen-cage-type chaperones to emphasize that they provide a closed, protected environment to help the folding of their substrates, our understanding of the molecular mechanism of how these chaperones help protein folding is still incomplete. The present study adds two novel elements to the mechanism of how Anfinsen-cage-type chaperones (members of the 60 kDa chaperone family) aid protein folding. It is proposed that (1) these chaperones do not generally unfold their targets, but by a multidirectional expansion preferentially loosen the tight, inner structure of the collapsed target protein; and (2) during the expansion water molecules enter the hydrophobic core of the target, this percolation being a key step in chaperone action. This study compares this chaperone-percolator model with existing explanations and suggests further experiments to test it. BioEssays 1999;21:959-965. Copyright 1999 John Wiley & Sons, Inc.