1yt2
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Crystal Structure of the Unliganded Form of GRP94, the ER Hsp90: Basis for Nucleotide-Induced Conformational Change, GRP94N APO CRYSTAL
OverviewOverview
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.
About this StructureAbout this Structure
1YT2 is a Single protein structure of sequence from Canis lupus familiaris with PG4 as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Structure of unliganded GRP94, the endoplasmic reticulum Hsp90. Basis for nucleotide-induced conformational change., Dollins DE, Immormino RM, Gewirth DT, J Biol Chem. 2005 Aug 26;280(34):30438-47. Epub 2005 Jun 11. PMID:15951571
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