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Nucleotide Exchange Factors for Hsp70 Molecular Chaperones: GrpE, Hsp110/Grp170, HspBP1/Sil1, and BAG Domain Proteins

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The Networking of Chaperones by Co-Chaperones

Part of the book series: Subcellular Biochemistry ((SCBI,volume 101))

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 (NEFs) facilitate the conversion from the ADP-bound to the ATP-bound state, thus closing the chaperone folding cycle. NEF function can additionally be antagonized by ADP dissociation inhibitors. Beginning with the discovery of the prototypical bacterial NEF, GrpE, a large diversity of nucleotide exchange factors for Hsp70 have been identified, connecting it to a multitude of cellular processes in the eukaryotic cell. Here we review recent advances toward 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 cellular quality control and degradation pathways.

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Authors and Affiliations

  1. Department of Cellular Biochemistry, Max-Planck-Institute of Biochemistry, Martinsried, Germany

    Andreas Bracher & Jacob Verghese

  2. Trophic Communications GmbH, Munich, Germany

    Jacob Verghese

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  1. Andreas Bracher
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  2. Jacob Verghese
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Correspondence to Andreas Bracher .

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

    Adrienne L. Edkins

  2. Faculty of Health Sciences, Higher Colleges of Technology, Sharjah, United Arab Emirates

    Gregory L. Blatch

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Bracher, A., Verghese, J. (2023). Nucleotide Exchange Factors for Hsp70 Molecular Chaperones: GrpE, Hsp110/Grp170, HspBP1/Sil1, and BAG Domain Proteins. In: Edkins, A.L., Blatch, G.L. (eds) The Networking of Chaperones by Co-Chaperones. Subcellular Biochemistry, vol 101. Springer, Cham. https://doi.org/10.1007/978-3-031-14740-1_1

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