7zr6

From Proteopedia

(Difference between revisions)

Current revision

CryoEM structure of HSP90-CDC37-BRAF(V600E)-PP5(open) complex

Structural highlights

7zr6 is a 5 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 4.2Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

HS90B_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.^[1] ^[2]

Publication Abstract from PubMed

Activation of client protein kinases by the HSP90 molecular chaperone system is affected by phosphorylation at multiple sites on HSP90, the kinase-specific co-chaperone CDC37, and the kinase client itself. Removal of regulatory phosphorylation from client kinases and their release from the HSP90-CDC37 system depends on the Ser/Thr phosphatase PP5, which associates with HSP90 via its N-terminal TPR domain. Here, we present the cryoEM structure of the oncogenic protein kinase client BRAF(V600E) bound to HSP90-CDC37, showing how the V600E mutation favours BRAF association with HSP90-CDC37. Structures of HSP90-CDC37-BRAF(V600E) complexes with PP5 in autoinhibited and activated conformations, together with proteomic analysis of its phosphatase activity on BRAF(V600E) and CRAF, reveal how PP5 is activated by recruitment to HSP90 complexes. PP5 comprehensively dephosphorylates client proteins, removing interaction sites for regulatory partners such as 14-3-3 proteins and thus performing a 'factory reset' of the kinase prior to release.

HSP90-CDC37-PP5 forms a structural platform for kinase dephosphorylation.,Oberoi J, Guiu XA, Outwin EA, Schellenberger P, Roumeliotis TI, Choudhary JS, Pearl LH Nat Commun. 2022 Nov 29;13(1):7343. doi: 10.1038/s41467-022-35143-2. PMID:36446791^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Chadli A, Graham JD, Abel MG, Jackson TA, Gordon DF, Wood WM, Felts SJ, Horwitz KB, Toft D. GCUNC-45 is a novel regulator for the progesterone receptor/hsp90 chaperoning pathway. Mol Cell Biol. 2006 Mar;26(5):1722-30. PMID:16478993 doi:http://dx.doi.org/26/5/1722
↑ Retzlaff M, Stahl M, Eberl HC, Lagleder S, Beck J, Kessler H, Buchner J. Hsp90 is regulated by a switch point in the C-terminal domain. EMBO Rep. 2009 Oct;10(10):1147-53. Epub 2009 Aug 21. PMID:19696785 doi:http://dx.doi.org/embor2009153
↑ Oberoi J, Guiu XA, Outwin EA, Schellenberger P, Roumeliotis TI, Choudhary JS, Pearl LH. HSP90-CDC37-PP5 forms a structural platform for kinase dephosphorylation. Nat Commun. 2022 Nov 29;13(1):7343. doi: 10.1038/s41467-022-35143-2. PMID:36446791 doi:http://dx.doi.org/10.1038/s41467-022-35143-2

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7zr6"

Categories: Homo sapiens | Large Structures | Oberoi J | Pearl LH

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[7zr6]] is a 5 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=7ZR6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZR6 FirstGlance]. <br>
-</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=SEP:PHOSPHOSERINE'>SEP</scene></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]] 4.2&#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=SEP:PHOSPHOSERINE'>SEP</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=7zr6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zr6 OCA], [https://pdbe.org/7zr6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zr6 RCSB], [https://www.ebi.ac.uk/pdbsum/7zr6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zr6 ProSAT]</span></td></tr>
 </table>
@@ Line 18: / Line 19: @@
 </div>
 <div class="pdbe-citations 7zr6" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Heat Shock Protein structures|Heat Shock Protein structures]]
+*[[Protein phosphatase 3D structures|Protein phosphatase 3D structures]]
 == References ==
 <references/>

7zr6

From Proteopedia

Current revision

CryoEM structure of HSP90-CDC37-BRAF(V600E)-PP5(open) complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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