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, Vincent Guerriero, F. Ulrich Hartl, Andreas Bracher

Research output: Contribution to journalArticle

139 Citations (Scopus)

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

Fingerprint

Nucleotides
Adenosine Triphosphatases
Armadillos
Protein Folding
Cytosol
Saccharomyces cerevisiae
Proteins

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Shomura, Y., Dragovic, Z., Chang, H. C., Tzvetkov, N., Young, J. C., Brodsky, J. L., ... 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

Regulation of Hsp70 function by HspBP1 : Structural analysis reveals an alternate mechanism for Hsp70 nucleotide exchange. / Shomura, Yasuhito; Dragovic, Zdravko; Chang, Hung Chun; Tzvetkov, Nikolay; Young, Jason C.; Brodsky, Jeffrey L.; Guerriero, Vincent; Hartl, F. Ulrich; Bracher, Andreas.

In: Molecular Cell, Vol. 17, No. 3, 04.02.2005, p. 367-379.

Research output: Contribution to journalArticle

Shomura, Y, Dragovic, Z, Chang, HC, Tzvetkov, N, Young, JC, Brodsky, JL, Guerriero, V, Hartl, FU & Bracher, A 2005, 'Regulation of Hsp70 function by HspBP1: Structural analysis reveals an alternate mechanism for Hsp70 nucleotide exchange', Molecular Cell, vol. 17, no. 3, pp. 367-379. https://doi.org/10.1016/j.molcel.2004.12.023
Shomura, Yasuhito ; Dragovic, Zdravko ; Chang, Hung Chun ; Tzvetkov, Nikolay ; Young, Jason C. ; Brodsky, Jeffrey L. ; Guerriero, Vincent ; Hartl, F. Ulrich ; Bracher, Andreas. / Regulation of Hsp70 function by HspBP1 : Structural analysis reveals an alternate mechanism for Hsp70 nucleotide exchange. In: Molecular Cell. 2005 ; Vol. 17, No. 3. pp. 367-379.
@article{23d752a2c4284577a4aac4cf29c6284b,
title = "Regulation of Hsp70 function by HspBP1: Structural analysis reveals an alternate mechanism for Hsp70 nucleotide exchange",
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.",
author = "Yasuhito Shomura and Zdravko Dragovic and Chang, {Hung Chun} and Nikolay Tzvetkov and Young, {Jason C.} and Brodsky, {Jeffrey L.} and Vincent Guerriero and Hartl, {F. Ulrich} and Andreas Bracher",
year = "2005",
month = "2",
day = "4",
doi = "10.1016/j.molcel.2004.12.023",
language = "English (US)",
volume = "17",
pages = "367--379",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "3",

}

TY - JOUR

T1 - Regulation of Hsp70 function by HspBP1

T2 - Structural analysis reveals an alternate mechanism for Hsp70 nucleotide exchange

AU - Shomura, Yasuhito

AU - Dragovic, Zdravko

AU - Chang, Hung Chun

AU - Tzvetkov, Nikolay

AU - Young, Jason C.

AU - Brodsky, Jeffrey L.

AU - Guerriero, Vincent

AU - Hartl, F. Ulrich

AU - Bracher, Andreas

PY - 2005/2/4

Y1 - 2005/2/4

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=13244278043&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=13244278043&partnerID=8YFLogxK

U2 - 10.1016/j.molcel.2004.12.023

DO - 10.1016/j.molcel.2004.12.023

M3 - Article

C2 - 15694338

AN - SCOPUS:13244278043

VL - 17

SP - 367

EP - 379

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 3

ER -