1YSZ

Crystal Structure of the Unliganded Form of GRP94, the ER Hsp90: Basis for Nucleotide-Induced Conformational Change, GRP94N(DELTA)41 APO CRYSTAL SOAKED WITH NECA

Summary for 1YSZ

• Entry DOI: 10.2210/pdb1ysz/pdb
• Related: 1QY5 1TBW 1TC0 1TC6 1U2O 1YT0 1YT1 1YT2
• Descriptor: Endoplasmin, N-ETHYL-5'-CARBOXAMIDO ADENOSINE, TETRAETHYLENE GLYCOL, ... (4 entities in total)
• Functional Keywords: grp94, gp96, hsp90, bergerat, chaperone, endoplasmic reticulum, neca, htpg
• Biological source: Canis lupus familiaris (dog); More
• Cellular location: Endoplasmic reticulum lumen: P41148
• Total number of polymer chains: 1
• Total formula weight: 27404.98

Authors

Dollins, D.E.,Immormino, R.M.,Gewirth, D.T. (deposition date: 2005-02-09, release date: 2005-06-14, Last modification date: 2023-08-23)

Primary citation

Dollins, D.E.,Immormino, R.M.,Gewirth, D.T.
Structure of Unliganded GRP94, the Endoplasmic Reticulum Hsp90: BASIS FOR NUCLEOTIDE-INDUCED CONFORMATIONAL CHANGE
J.Biol.Chem., 280:30438-30447, 2005

PubMed Abstract: GRP94, the endoplasmic reticulum paralog of Hsp90, is regulated by adenosine nucleotides that bind to its N-terminal regulatory domain. Because of its weak affinity for nucleotides, the functionally relevant transition in GRP94 is likely to be between the unliganded and nucleotide-bound states. We have determined the structure of the unliganded GRP94 N-domain. The helix 1-4-5 subdomain of the unliganded protein adopts the closed conformation seen in the structure of the protein in complex with inhibitors. This conformation is distinct from the open conformation of the subdomain seen when the protein is bound to ATP or ADP. ADP soaked into crystals of the unliganded protein reveals an intermediate conformation midway between the open and closed states and demonstrates that in GRP94 the conversion between the open and closed states is driven by ligand binding. The direction of the observed movement in GRP94 shows that nucleotides act to open the subdomain elements rather than close them, which is contrary to the motion proposed for Hsp90. These observations support a model where ATP binding dictates the conformation of the N-domain and regulates its ability to form quaternary structural interactions.

PubMed: 15951571
DOI: 10.1074/jbc.M503761200

Experimental method

X-RAY DIFFRACTION (2.65 Å)