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 language | English (US) |
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Pages (from-to) | 367-379 |
Number of pages | 13 |
Journal | Molecular cell |
Volume | 17 |
Issue number | 3 |
DOIs | |
State | Published - Feb 4 2005 |
Externally published | Yes |
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
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Dive into the research topics of 'Regulation of Hsp70 function by HspBP1: Structural analysis reveals an alternate mechanism for Hsp70 nucleotide exchange'. Together they form a unique fingerprint.Datasets
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Crystal structure of the HspBP1 core domain complexed with the fragment of Hsp70 ATPase domain
Shomura, Y. (Contributor), Dragovic, Z. (Contributor), Chang, H.-C. (Contributor), Tzvetkov, N. (Contributor), Young, J. C. (Contributor), Brodsky, J. L. (Contributor), Guerriero, V. (Contributor), Hartl, F. U. (Contributor) & Bracher, A. (Contributor), Protein Data Bank (PDB), Mar 1 2005
DOI: 10.2210/pdb1XQS/pdb, https://www.wwpdb.org/pdb?id=pdb_00001xqs
Dataset
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Crystal structure of the HspBP1 core domain
Shomura, Y. (Contributor), Dragovic, Z. (Contributor), Chang, H.-C. (Contributor), Tzvetkov, N. (Contributor), Young, J. C. (Contributor), Brodsky, J. L. (Contributor), Guerriero, V. (Contributor), Hartl, F. U. (Contributor) & Bracher, A. (Contributor), Protein Data Bank (PDB), Mar 1 2005
DOI: 10.2210/pdb1XQR/pdb, https://www.wwpdb.org/pdb?id=pdb_00001xqr
Dataset