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 journalArticlepeer-review

    162 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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