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==The GR-Maturation Complex: Glucocorticoid Receptor in complex with Hsp90 and co-chaperone p23==
<StructureSection load='7krj' size='340' side='right'caption='[[7krj]], [[Resolution|resolution]] 2.56&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7krj]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KRJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KRJ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.56&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=DEX:DEXAMETHASONE'>DEX</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7krj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7krj OCA], [https://pdbe.org/7krj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7krj RCSB], [https://www.ebi.ac.uk/pdbsum/7krj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7krj ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HS90A_HUMAN HS90A_HUMAN] Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function.<ref>PMID:15937123</ref> <ref>PMID:11274138</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Hsp90 is a conserved and essential molecular chaperone responsible for the folding and activation of hundreds of 'client' proteins(1-3). The glucocorticoid receptor (GR) is a model client that constantly depends on Hsp90 for activity(4-9). GR ligand binding was previously shown to nr inhibited by Hsp70 and restored by Hsp90, aided by the co-chaperone p23(10). However, a molecular understanding of the chaperone-mediated remodelling that occurs between the inactive Hsp70-Hsp90 'client-loading complex' and an activated Hsp90-p23 'client-maturation complex' is lacking for any client, including GR. Here we present a cryo-electron microscopy (cryo-EM) structure of the human GR-maturation complex (GR-Hsp90-p23), revealing that the GR ligand-binding domain is restored to a folded, ligand-bound conformation, while being simultaneously threaded through the Hsp90 lumen. In addition, p23 directly stabilizes native GR using a C-terminal helix, resulting in enhanced ligand binding. This structure of a client bound to Hsp90 in a native conformation contrasts sharply with the unfolded kinase-Hsp90 structure(11). Thus, aided by direct co-chaperone-client interactions, Hsp90 can directly dictate client-specific folding outcomes. Together with the GR-loading complex structure(12), we present the molecular mechanism of chaperone-mediated GR remodelling, establishing the first, to our knowledge, complete chaperone cycle for any Hsp90 client.

Structure of Hsp90-p23-GR reveals the Hsp90 client-remodelling mechanism.,Noddings CM, Wang RY, Johnson JL, Agard DA Nature. 2022 Jan;601(7893):465-469. doi: 10.1038/s41586-021-04236-1. Epub 2021 , Dec 22. PMID:34937936<ref>PMID:34937936</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7krj" style="background-color:#fffaf0;"></div>

==See Also==
*[[Glucocorticoid receptor 3D structures|Glucocorticoid receptor 3D structures]]
*[[Heat Shock Protein structures|Heat Shock Protein structures]]
*[[Prostaglandin E synthase|Prostaglandin E synthase]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Agard DA]]
[[Category: Noddings CM]]
[[Category: Wang Y-R]]