View source for 5fwk


==Atomic cryoEM structure of Hsp90-Cdc37-Cdk4 complex==
<SX load='5fwk' size='340' side='right' viewer='molstar' caption='[[5fwk]], [[Resolution|resolution]] 3.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5fwk]] 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=5FWK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FWK 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]] 3.9&#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=MG:MAGNESIUM+ION'>MG</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=5fwk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fwk OCA], [https://pdbe.org/5fwk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5fwk RCSB], [https://www.ebi.ac.uk/pdbsum/5fwk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5fwk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HS90B_HUMAN 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.<ref>PMID:16478993</ref> <ref>PMID:19696785</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The Hsp90 molecular chaperone and its Cdc37 cochaperone help stabilize and activate more than half of the human kinome. However, both the mechanism by which these chaperones assist their "client" kinases and the reason why some kinases are addicted to Hsp90 while closely related family members are independent are unknown. Our structural understanding of these interactions is lacking, as no full-length structures of human Hsp90, Cdc37, or either of these proteins with a kinase have been elucidated. Here we report a 3.9 angstrom cryo-electron microscopy structure of the Hsp90-Cdc37-Cdk4 kinase complex. Surprisingly, the two lobes of Cdk4 are completely separated with the beta4-beta5 sheet unfolded. Cdc37 mimics part of the kinase N lobe, stabilizing an open kinase conformation by wedging itself between the two lobes. Finally, Hsp90 clamps around the unfolded kinase beta5 strand and interacts with exposed N- and C-lobe interfaces, protecting the kinase in a trapped unfolded state. On the basis of this structure and an extensive amount of previously collected data, we propose unifying conceptual and mechanistic models of chaperone-kinase interactions.

Atomic structure of Hsp90-Cdc37-Cdk4 reveals that Hsp90 traps and stabilizes an unfolded kinase.,Verba KA, Wang RY, Arakawa A, Liu Y, Shirouzu M, Yokoyama S, Agard DA Science. 2016 Jun 24;352(6293):1542-7. doi: 10.1126/science.aaf5023. PMID:27339980<ref>PMID:27339980</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5fwk" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cyclin-dependent kinase 3D structures|Cyclin-dependent kinase 3D structures]]
*[[Heat Shock Protein structures|Heat Shock Protein structures]]
== References ==
<references/>
__TOC__
</SX>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Agard DA]]
[[Category: Arakawa A]]
[[Category: Liu Y]]
[[Category: Verba KA]]
[[Category: Wang RYR]]
[[Category: Yokoyama S]]