2O1W

Structure of N-terminal plus middle domains (N+M) of GRP94

Summary for 2O1W

• Entry DOI: 10.2210/pdb2o1w/pdb
• Related: 1YT1 2O1T 2O1U 2O1V
• Descriptor: Endoplasmin (1 entity in total)
• Functional Keywords: grp94, hsp82, hsp90, htpg, chaperone, gp96, endoplasmin
• Biological source: Canis lupus familiaris (dog); More
• Cellular location: Endoplasmic reticulum lumen: P41148
• Total number of polymer chains: 5
• Total formula weight: 290879.74

Authors

Dollins, D.E.,Warren, J.J.,Immormino, R.M.,Gewirth, D.T. (deposition date: 2006-11-29, release date: 2007-10-23, Last modification date: 2023-08-30)

Primary citation

Dollins, D.E.,Warren, J.J.,Immormino, R.M.,Gewirth, D.T.
Structures of GRP94-Nucleotide Complexes Reveal Mechanistic Differences between the hsp90 Chaperones.
Mol.Cell, 28:41-56, 2007

PubMed Abstract: 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.

PubMed: 17936703
DOI: 10.1016/j.molcel.2007.08.024

Experimental method

X-RAY DIFFRACTION (3.4 Å)