7l7j: Difference between revisions
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==== | ==Cryo-EM structure of Hsp90:p23 closed-state complex== | ||
<StructureSection load='7l7j' size='340' side='right'caption='[[7l7j]]' scene=''> | <StructureSection load='7l7j' size='340' side='right'caption='[[7l7j]], [[Resolution|resolution]] 3.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[7l7j]] is a 3 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=7L7J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7L7J FirstGlance]. <br> | ||
</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=7l7j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7l7j OCA], [https://pdbe.org/7l7j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7l7j RCSB], [https://www.ebi.ac.uk/pdbsum/7l7j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7l7j ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.1Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</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=7l7j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7l7j OCA], [https://pdbe.org/7l7j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7l7j RCSB], [https://www.ebi.ac.uk/pdbsum/7l7j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7l7j ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/TEBP_HUMAN TEBP_HUMAN] Molecular chaperone that localizes to genomic response elements in a hormone-dependent manner and disrupts receptor-mediated transcriptional activation, by promoting disassembly of transcriptional regulatory complexes.<ref>PMID:11274138</ref> <ref>PMID:12077419</ref> <ref>PMID:10922363</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The Hsp90 chaperone promotes folding and activation of hundreds of client proteins in the cell through an ATP-dependent conformational cycle guided by distinct cochaperone regulators. The FKBP51 immunophilin binds Hsp90 with its tetratricopeptide repeat (TPR) domain and catalyzes peptidyl-prolyl isomerase (PPIase) activity during folding of kinases, nuclear receptors, and tau. Here we determined the cryoelectron microscopy (cryo-EM) structure of the human Hsp90:FKBP51:p23 complex to 3.3 A, which, together with mutagenesis and crosslinking analyses, reveals the basis for cochaperone binding to Hsp90 during client maturation. A helix extension in the TPR functions as a key recognition element, interacting across the Hsp90 C-terminal dimer interface presented in the closed, ATP conformation. The PPIase domain is positioned along the middle domain, adjacent to Hsp90 client binding sites, whereas a single p23 makes stabilizing interactions with the N-terminal dimer. With this architecture, FKBP51 is positioned to act on specific client residues presented during Hsp90-catalyzed remodeling. | |||
The structure of an Hsp90-immunophilin complex reveals cochaperone recognition of the client maturation state.,Lee K, Thwin AC, Nadel CM, Tse E, Gates SN, Gestwicki JE, Southworth DR Mol Cell. 2021 Sep 2;81(17):3496-3508.e5. doi: 10.1016/j.molcel.2021.07.023. Epub , 2021 Aug 10. PMID:34380015<ref>PMID:34380015</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7l7j" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Heat Shock Protein structures|Heat Shock Protein structures]] | |||
*[[Insulin 3D Structures|Insulin 3D Structures]] | |||
*[[Prostaglandin E synthase|Prostaglandin E synthase]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Gates SN]] | ||
[[Category: Lee K]] | |||
[[Category: Southworth DR]] | |||
[[Category: Thwin AC]] | |||
[[Category: Tse E]] | |||
Latest revision as of 22:37, 29 May 2024
Cryo-EM structure of Hsp90:p23 closed-state complexCryo-EM structure of Hsp90:p23 closed-state complex
Structural highlights
FunctionTEBP_HUMAN Molecular chaperone that localizes to genomic response elements in a hormone-dependent manner and disrupts receptor-mediated transcriptional activation, by promoting disassembly of transcriptional regulatory complexes.[1] [2] [3] Publication Abstract from PubMedThe Hsp90 chaperone promotes folding and activation of hundreds of client proteins in the cell through an ATP-dependent conformational cycle guided by distinct cochaperone regulators. The FKBP51 immunophilin binds Hsp90 with its tetratricopeptide repeat (TPR) domain and catalyzes peptidyl-prolyl isomerase (PPIase) activity during folding of kinases, nuclear receptors, and tau. Here we determined the cryoelectron microscopy (cryo-EM) structure of the human Hsp90:FKBP51:p23 complex to 3.3 A, which, together with mutagenesis and crosslinking analyses, reveals the basis for cochaperone binding to Hsp90 during client maturation. A helix extension in the TPR functions as a key recognition element, interacting across the Hsp90 C-terminal dimer interface presented in the closed, ATP conformation. The PPIase domain is positioned along the middle domain, adjacent to Hsp90 client binding sites, whereas a single p23 makes stabilizing interactions with the N-terminal dimer. With this architecture, FKBP51 is positioned to act on specific client residues presented during Hsp90-catalyzed remodeling. The structure of an Hsp90-immunophilin complex reveals cochaperone recognition of the client maturation state.,Lee K, Thwin AC, Nadel CM, Tse E, Gates SN, Gestwicki JE, Southworth DR Mol Cell. 2021 Sep 2;81(17):3496-3508.e5. doi: 10.1016/j.molcel.2021.07.023. Epub , 2021 Aug 10. PMID:34380015[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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