2O1W: Structure Of N-terminal Plus Middle Domains (n+m) Of Grp94

GRP94, an essential endoplasmic reticulum chaperone, is required for the conformational maturation of proteins destined for cell-surface display or export. The extent to which GRP94 and its cytosolic paralog, Hsp90, share a common mechanism remains controversial. GRP94 has not been shown conclusively to hydrolyze ATP or bind cochaperones, and both activities, by contrast, result in conformational changes and N-terminal dimerization in Hsp90 that are critical for its function. Here, we report the 2.4 A crystal structure of mammalian GRP94 in complex with AMPPNP and ADP. The chaperone is conformationally insensitive to the identity of the bound nucleotide, adopting a "twisted V" conformation that precludes N-terminal domain dimerization. We also present conclusive evidence that GRP94 possesses ATPase activity. Our observations provide a structural explanation for GRP94's observed rate of ATP hydrolysis and suggest a model for the role of ATP binding and hydrolysis in the GRP94 chaperone cycle.
PDB ID: 2O1WDownload
MMDB ID: 60119
PDB Deposition Date: 2006/11/29
Updated in MMDB: 2007/11
Experimental Method:
x-ray diffraction
Resolution: 3.4  Å
Source Organism:
Similar Structures:
Biological Unit for 2O1W: monomeric; determined by author
Molecular Components in 2O1W
Label Count Molecule
Protein (1 molecule)
Endoplasmin(Gene symbol: HSP90B1)
Molecule annotation
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Citing MMDB