Molecular chaperones in protein folding and translocation

Abstract

Chaperonin cpn60 and heat shock protein hsp70 couple their ATPase cycles to the binding and dissociation of non-native proteins. cpn60 is a cylindrical tetradecamer that uses a co-protein (cpn10) and both positive and negative cooperativity to alter the properties of its two voluminous protein-binding chambers in an alternating, asymmetric cycle. In the hsp70 reaction cycle, short segments of polypeptide bind rapidly and weakly to the ATP state, so triggering hydrolysis and consequent stabilization of the complex. Co-proteins of the hsp40 family enhance this partial reaction, whereas nucleotide exchange factors destabilize the product. The individual steps in the two energy transducing mechanisms have only recently been elucidated and provide us with a more detailed picture of the way in which these chaperones can influence the folding, assembly and translocation of protein structures in the cell.