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

被引:155
作者
Shomura, Y
Dragovic, Z
Chang, HC
Tzvetkov, N
Young, JC
Brodsky, JL
Guerriero, V
Hartl, FU
Bracher, A
机构
[1] Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA
[2] Univ Arizona, Dept Anim Sci, Tucson, AZ 85721 USA
[3] Univ Arizona, Dept Mol & Cellular Biol, Tucson, AZ 85721 USA
关键词
D O I
10.1016/j.molcel.2004.12.023
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 37degreesC. 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 alpha-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.
引用
收藏
页码:367 / 379
页数:13
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