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Specification of Hsp70 Function by Type I and Type II Hsp40

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The Networking of Chaperones by Co-chaperones

Part of the book series: Subcellular Biochemistry ((SCBI,volume 78))

Abstract

Cellular homeostasis and stress survival requires maintenance of the proteome and suppression of proteotoxicity. Molecular chaperones promote cell survival through repair of misfolded proteins and cooperation with protein degradation machines to discard terminally damaged proteins. Hsp70 family members play an essential role in cellular protein metabolism by binding and releasing nonnative proteins to facilitate protein folding, refolding and degradation. Hsp40 family members are Hsp70 co-chaperones that determine the fate of Hsp70 clients by facilitating protein folding, assembly, and degradation. Hsp40s select substrates for Hsp70 via use of an intrinsic chaperone activity to bind non-native regions of proteins. During delivery of bound cargo Hsp40s employ a conserved J-domain to stimulate Hsp70 ATPase activity and thereby stabilize complexes between Hsp70 and non-native proteins. Type I and Type II Hsp40s direct Hsp70 to preform multiple functions in protein homeostasis. This review describes the mechanisms by which Type I and Type II sub-types of Hsp40 bind and deliver substrates to Hsp70.

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Acknowledgements

Work in the laboratory of DMC is supported by the National Institutes of Health 5R01GM056981. CHR is supported by Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP), Ministério da Ciência e Tecnologia/Conselho Nacional de Pesquisa e Desenvolvimento (MCT/CNPq), and NIH-R03TW007437 through the Fogarty International Center.

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Authors and Affiliations

  1. Department of Cell Biology and Physiology, School of Medicine, University of North Carolina, 27599, Chapel Hill, NC, USA

    Douglas M. Cyr

  2. Department of Organic Chemistry, Institute of Chemistry,, University of Campinas-UNICAMP, 13083-970, Campinas—SP, Brazil

    Carlos H. Ramos

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  1. Douglas M. Cyr
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  2. Carlos H. Ramos
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Correspondence to Douglas M. Cyr .

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Editors and Affiliations

  1. Victoria University, College of Health and Biomedicine, Melbourne, Victoria, Australia

    Gregory Lloyd Blatch

  2. Department of Biochemistry and Microbiology, Rhodes University, Biomedical Biotechnology Research Unit, Grahamstown, South Africa

    Adrienne Lesley Edkins

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Cyr, D., Ramos, C. (2015). Specification of Hsp70 Function by Type I and Type II Hsp40. In: Blatch, G., Edkins, A. (eds) The Networking of Chaperones by Co-chaperones. Subcellular Biochemistry, vol 78. Springer, Cham. https://doi.org/10.1007/978-3-319-11731-7_4

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