1TC0

Ligand Induced Conformational Shifts in the N-terminal Domain of GRP94, Open Conformation Complexed with the physiological partner ATP

Summary for 1TC0

• Entry DOI: 10.2210/pdb1tc0/pdb
• Related: 1QY5 1QY8 1QYE 1QYH 1TBW 1TC6
• Descriptor: Endoplasmin, MAGNESIUM ION, ADENOSINE-5'-TRIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: grp94, hsp90, atp, bergerat, chaperone, endoplasmic reticulum
• Biological source: Canis lupus familiaris (dog); More
• Cellular location: Endoplasmic reticulum lumen: P41148
• Total number of polymer chains: 2
• Total formula weight: 55062.13

Authors

Gewirth, D.T.,Immormino, R.M.,Dollins, D.E.,Shaffer, P.L.,Walker, M.A.,Soldano, K.L. (deposition date: 2004-05-20, release date: 2004-08-24, Last modification date: 2024-02-14)

Primary citation

Immormino, R.M.,Dollins, D.E.,Shaffer, P.L.,Soldano, K.L.,Walker, M.A.,Gewirth, D.T.
Ligand-induced Conformational Shift in the N-terminal Domain of GRP94, an Hsp90 Chaperone.
J.Biol.Chem., 279:46162-46171, 2004

PubMed Abstract: 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.

PubMed: 15292259
DOI: 10.1074/jbc.M405253200

Experimental method

X-RAY DIFFRACTION (2.2 Å)