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Publication Abstract from PubMed

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.

Ligand-induced conformational shift in the N-terminal domain of GRP94, an Hsp90 chaperone.,Immormino RM, Dollins DE, Shaffer PL, Soldano KL, Walker MA, Gewirth DT J Biol Chem. 2004 Oct 29;279(44):46162-71. Epub 2004 Aug 2. PMID:15292259^[1]

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