Regulation of Hsp70 function by HspBP1: Structural analysis reveals an alternate mechanism for Hsp70 nucleotide exchange

Yasuhito Shomura, Zdravko Dragovic, Hung Chun Chang, Nikolay Tzvetkov, Jason C. Young, Jeffrey L. Brodsky, Vince Guerriero, F. Ulrich Hartl, Andreas Bracher

Research output: Contribution to journalArticle

147 Scopus citations

Abstract

HspBP1 belongs to a family of eukaryotic proteins recently identified as nucleotide exchange factors for Hsp70. We show that the S. cerevisiae ortholog of HspBP1, Fes1p, is required for efficient protein folding in the cytosol at 37°C. The crystal structure of HspBP1, alone and complexed with part of the Hsp70 ATPase domain, reveals a mechanism for its function distinct from that of BAG-1 or GrpE, previously characterized nucleotide exchange factors of Hsp70. HspBP1 has a curved, all α-helical fold containing four armadillo-like repeats unlike the other nucleotide exchange factors. The concave face of HspBP1 embraces lobe II of the ATPase domain, and a steric conflict displaces lobe I, reducing the affinity for nucleotide. In contrast, BAG-1 and GrpE trigger a conserved conformational change in lobe II of the ATPase domain. Thus, nucleotide exchange on eukaryotic Hsp70 occurs through two distinct mechanisms.

Original languageEnglish (US)
Pages (from-to)367-379
Number of pages13
JournalMolecular cell
Volume17
Issue number3
DOIs
StatePublished - Feb 4 2005

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Shomura, Y., Dragovic, Z., Chang, H. C., Tzvetkov, N., Young, J. C., Brodsky, J. L., Guerriero, V., Hartl, F. U., & Bracher, A. (2005). Regulation of Hsp70 function by HspBP1: Structural analysis reveals an alternate mechanism for Hsp70 nucleotide exchange. Molecular cell, 17(3), 367-379. https://doi.org/10.1016/j.molcel.2004.12.023