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Abstract:
Molecular chaperones of the Hsp70 family are key components of the cellular protein folding machinery. Substrate folding is accomplished by iterative cycles of ATP binding, hydrolysis and release. The ATPase activity of Hsp70 is regulated by two main classes of cochaperones: J-domain proteins stimulate ATPase hydrolysis by Hsp70, while nucleotide exchange factors (NEF) facilitate its conversion from the ADP-bound to the ATP-bound state, thus closing the chaperone folding cycle. Beginning with the discovery of the prototypical bacterial NEF GrpE, a large diversity of Hsp70 nucleotide exchange factors has been identified, connecting Hsp70 to a multitude of cellular processes in the eukaryotic cell. Here we review recent advances towards structure and function of nucleotide exchange factors from the Hsp110/Grp170, HspBP1/Sil1 and BAG domain protein families and discuss how these cochaperones connect protein folding with quality control and degradation pathways.
