Crystal structure of the HspBP1 core domain complexed with the fragment of Hsp70 ATPase domain
[HPBP1_HUMAN] Inhibits HSPA1A chaperone activity by changing the conformation of the ATP-binding domain of HSPA1A and interfering with ATP binding. Interferes with ubiquitination mediated by STUB1 and inhibits chaperone-assisted degradation of immature CFTR.   
Publication Abstract from PubMed
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 degrees 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 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.
Regulation of Hsp70 function by HspBP1: structural analysis reveals an alternate mechanism for Hsp70 nucleotide exchange.,Shomura Y, Dragovic Z, Chang HC, Tzvetkov N, Young JC, Brodsky JL, Guerriero V, Hartl FU, Bracher A Mol Cell. 2005 Feb 4;17(3):367-79. PMID:15694338
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.