Mechanisms of the Hsp70 chaperone systemThis paper is one of a selection of papers published in this special issue entitled “Canadian Society of Biochemistry, Molecular & Cellular Biology 52nd Annual Meeting — Protein Folding: Principles and Diseases” and has undergone the Journal's usual peer review process.

Abstract

Molecular chaperones of the Hsp70 family have diverse functions in cells. They assist the folding of newly synthesized and stress-denatured proteins, as well as the import of proteins into organelles, and the dissociation of aggregated proteins. The well-conserved Hsp70 chaperones are ATP dependent: binding and hydrolysis of ATP regulates their interactions with unfolded polypeptide substrates, and ATPase cycling is necessary for their function. All cellular functions of Hsp70 chaperones use the same mechanism of ATP-driven polypeptide binding and release. The Hsp40 co-chaperones stimulate ATP hydrolysis by Hsp70 and the type 1 Hsp40 proteins are conserved from Escherichia coli to humans. Various nucleotide exchange factors also promote the Hsp70 ATPase cycle. Recent advances have added to our understanding of the Hsp70 mechanism at a molecular level.