The Hsp70 chaperone network

• Published in: Nature reviews. Molecular cell biology Vol. 20; no. 11; pp. 665 - 680
• Main Authors: Rosenzweig, Rina, Nillegoda, Nadinath B., Mayer, Matthias P., Bukau, Bernd
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2019; Nature Publishing Group
• Subjects: 631/80/470; 631/80/474/1768; Adenosine triphosphatase; Adenosine Triphosphatases - metabolism; Analysis; Animals; Biochemistry; Biomedical and Life Sciences; Cancer Research; Cell Biology; Chaperones; Chaperonins; Chemical compounds; Degradation; Developmental Biology; Disaggregation; Folding; Heat exchange; Heat shock proteins; Homeostasis; Hsp60 protein; HSP70 Heat-Shock Proteins - metabolism; Hsp70 protein; HSP90 Heat-Shock Proteins - metabolism; Hsp90 protein; Humans; Life Sciences; Molecular modelling; Molecular structure; Nucleotides; Organic chemistry; Physiological aspects; Protein Aggregates; Protein Domains; Protein Folding; Proteins; Review Article; Small heat shock proteins; Stem Cells; Substrates; Germany
• ISSN: 1471-0072; 1471-0080
• DOI: 10.1038/s41580-019-0133-3

The 70-kDa heat shock proteins (Hsp70s) are ubiquitous molecular chaperones that act in a large variety of cellular protein folding and remodelling processes. They function virtually at all stages of the life of proteins from synthesis to degradation and are thus crucial for maintaining protein homeostasis, with direct implications for human health. A large set of co-chaperones comprising J-domain proteins and nucleotide exchange factors regulate the ATPase cycle of Hsp70s, which is allosterically coupled to substrate binding and release. Moreover, Hsp70s cooperate with other cellular chaperone systems including Hsp90, Hsp60 chaperonins, small heat shock proteins and Hsp100 AAA+ disaggregases, together constituting a dynamic and functionally versatile network for protein folding, unfolding, regulation, targeting, aggregation and disaggregation, as well as degradation. In this Review we describe recent advances that have increased our understanding of the molecular mechanisms and working principles of the Hsp70 network. This knowledge showcases how the Hsp70 chaperone system controls diverse cellular functions, and offers new opportunities for the development of chemical compounds that modulate disease-related Hsp70 activities. The Hsp70 chaperones regulate protein metabolism, including folding, unfolding, subcellular localization, aggregation/disaggregation and incorporation into protein complexes. Recent studies have revealed the mechanisms of functions of Hsp70s and their co-chaperones, highlighting new opportunities for modulating disease-related Hsp70 roles.