Document Detail

Ligand-induced conformational shift in the N-terminal domain of GRP94, an Hsp90 chaperone.
MedLine Citation:
PMID:  15292259     Owner:  NLM     Status:  MEDLINE    
GRP94 is the endoplasmic reticulum paralog of cytoplasmic Hsp90. Models of Hsp90 action posit an ATP-dependent conformational switch in the N-terminal ligand regulatory domain of the chaperone. However, crystal structures of the isolated N-domain of Hsp90 in complex with a variety of ligands have yet to demonstrate such a conformational change. We have determined the structure of the N-domain of GRP94 in complex with ATP, ADP, and AMP. Compared with the N-ethylcarboxamidoadenosine and radicicol-bound forms, these structures reveal a large conformational rearrangement in the protein. The nucleotide-bound form exposes new surfaces that interact to form a biochemically plausible dimer that is reminiscent of those seen in structures of MutL and DNA gyrase. Weak ATP binding and a conformational change in response to ligand identity are distinctive mechanistic features of GRP94 and suggest a model for how GRP94 functions in the absence of co-chaperones and ATP hydrolysis.
Robert M Immormino; D Eric Dollins; Paul L Shaffer; Karen L Soldano; Melissa A Walker; Daniel T Gewirth
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Publication Detail:
Type:  Journal Article     Date:  2004-08-02
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  279     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-10-25     Completed Date:  2004-11-30     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  46162-71     Citation Subset:  IM    
Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA.
Data Bank Information
Bank Name/Acc. No.:
PDB/1TBW;  1TC0;  1TC6
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MeSH Terms
Adenosine Triphosphate / chemistry,  metabolism
DNA Gyrase / chemistry
HSP70 Heat-Shock Proteins / chemistry*
HSP90 Heat-Shock Proteins / chemistry
Membrane Proteins / chemistry*
Protein Conformation
Reg. No./Substance:
0/HSP70 Heat-Shock Proteins; 0/HSP90 Heat-Shock Proteins; 0/Ligands; 0/Membrane Proteins; 0/glucose-regulated proteins; 56-65-5/Adenosine Triphosphate; EC 5.99.1.-/DNA Gyrase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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