JBC Reviews
Recent advances in the structural and mechanistic aspects of Hsp70 molecular chaperones

https://doi.org/10.1074/jbc.REV118.002810Get rights and content
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Hsp70 chaperones are central hubs of the protein quality control network and collaborate with co-chaperones having a J-domain (an ∼70-residue–long helical hairpin with a flexible loop and a conserved His–Pro–Asp motif required for ATP hydrolysis by Hsp70s) and also with nucleotide exchange factors to facilitate many protein-folding processes that (re)establish protein homeostasis. The Hsp70s are highly dynamic nanomachines that modulate the conformation of their substrate polypeptides by transiently binding to short, mostly hydrophobic stretches. This interaction is regulated by an intricate allosteric mechanism. The J-domain co-chaperones target Hsp70 to their polypeptide substrates, and the nucleotide exchange factors regulate the lifetime of the Hsp70–substrate complexes. Significant advances in recent years are beginning to unravel the molecular mechanism of this chaperone machine and how they treat their substrate proteins.

molecular chaperone
70-kilodalton heat shock protein (Hsp70)
protein folding
allosteric regulation
chaperone DnaK (DnaK)
chaperone DnaJ (DnaJ)
nanomachine
J-domain
protein homeostasis

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This is the second article in the JBC Reviews series “Molecular chaperones and protein quality control.” The authors declare that they have no conflicts of interest with the contents of this article.