Sandbox Reserved 1472
From Proteopedia
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== Mechanics & Energetics == | == Mechanics & Energetics == | ||
| - | Hsp90 and the co-chaperone Cdc37 are responsible for about 60% of kinases to achieve an active state<ref>PMID:27339980</ref>. One of the questions that researchers have had is why some kinases are clients of Hsp90 and Cdc37 and not others. There is evidence Cdc37 works by recognizing conformational instability of kinase clients and changing their folding landscapes as it binds to the client and recruits it to Hsp90<ref>PMID:29267381</ref>. In this way Cdc37 would be selecting kinase clients for Hsp90, where less thermodynamically stable clients would be delivered to Hsp90 and more stable clients wold not. | + | Hsp90 and the co-chaperone Cdc37 are responsible for about 60% of kinases to achieve an active state<ref>PMID:27339980</ref>. One of the questions that researchers have had is why some kinases are clients of Hsp90 and Cdc37 and not others. There is evidence Cdc37 works by recognizing conformational instability of kinase clients and changing their folding landscapes as it binds to the client and recruits it to Hsp90<ref>PMID:29267381</ref>. In this way Cdc37 would be selecting kinase clients for Hsp90, where less thermodynamically stable clients would be delivered to Hsp90 and more stable clients wold not. |
| - | + | ||
== Relevance == | == Relevance == | ||
== Structural highlights == | == Structural highlights == | ||
| - | + | In the cryo-electron microscopy structure of the Hsp90-Cdc37-Cdk4 complex | |
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes. | This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes. | ||
<scene name='80/800651/Hsp90_homodimer/1'>Hsp90 homodimer</scene> <scene name='80/800651/Cdc37-cdk4_complex/4'>Cdc37-Cdk4 complex</scene> <scene name='80/800651/Hsp90-cdc37-cdk4_complex/1'>Hsp90-Cdc37-Cdk4 complex</scene> | <scene name='80/800651/Hsp90_homodimer/1'>Hsp90 homodimer</scene> <scene name='80/800651/Cdc37-cdk4_complex/4'>Cdc37-Cdk4 complex</scene> <scene name='80/800651/Hsp90-cdc37-cdk4_complex/1'>Hsp90-Cdc37-Cdk4 complex</scene> | ||
Revision as of 22:45, 4 December 2018
| This Sandbox is Reserved from November 5 2018 through January 1, 2019 for use in the course "CHEM 4923: Senior Project taught by Christina R. Bourne at the University of Oklahoma, Norman, USA. This reservation includes Sandbox Reserved 1471 through Sandbox Reserved 1478. |
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Hsp90-Cdc37-Cdk4 Complex
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Function
The Hsp90-Cdc37-Cdk4 complex is made up of the Heat Shock Protein 90 chaperone molecule, Cell Division Cycle 37 co-chaperone molecule, and the Cyclin-dependent 4 Kinase client molecule. Hsp90 is a 90-kDa protein that acts as a molecular chaperone for a variety of client proteins the majority of which are involved in signal transduction. It belongs to a group of proteins called heat shock proteins. Heat shock proteins are named for the response that organisms exhibit due to stresses at a cellular level such as elevated temperatures beyond the normal existing environment cells usually cope with. A major feature of this response is an alteration of an organism’s gene expression through increased heat shock protein production[1]. Cdc37 is one the the main co-chaperones of Hsp90, it recruits kinase proteins for late folding and activation by binding to the kinase and delivering it to Hsp90. Cdk4 is a part of a kinase complex that is needed for cell cycle G1 phase progression. For the activation of Cdk4 there must be proper folding, binding of the regulator cyclin D, ATP binding, a positioning of the active site near the ATP binding site and phosphorylation of the amino acid residue T172. Hsp90 and the co-chaperone Cdc37 plays a crucial role in the late folding process of Cdk4 needed for its activation of which is critical for cell development[2].
Mechanics & Energetics
Hsp90 and the co-chaperone Cdc37 are responsible for about 60% of kinases to achieve an active state[3]. One of the questions that researchers have had is why some kinases are clients of Hsp90 and Cdc37 and not others. There is evidence Cdc37 works by recognizing conformational instability of kinase clients and changing their folding landscapes as it binds to the client and recruits it to Hsp90[4]. In this way Cdc37 would be selecting kinase clients for Hsp90, where less thermodynamically stable clients would be delivered to Hsp90 and more stable clients wold not.
Relevance
Structural highlights
In the cryo-electron microscopy structure of the Hsp90-Cdc37-Cdk4 complex This is a sample scene created with SAT to by Group, and another to make of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes. </StructureSection>
References
- ↑ Hoter A, El-Sabban ME, Naim HY. The HSP90 Family: Structure, Regulation, Function, and Implications in Health and Disease. Int J Mol Sci. 2018 Aug 29;19(9). pii: ijms19092560. doi: 10.3390/ijms19092560. PMID:30158430 doi:http://dx.doi.org/10.3390/ijms19092560
- ↑ Radli M, Rudiger SGD. Dancing with the Diva: Hsp90-Client Interactions. J Mol Biol. 2018 Sep 14;430(18 Pt B):3029-3040. doi: 10.1016/j.jmb.2018.05.026., Epub 2018 May 18. PMID:29782836 doi:http://dx.doi.org/10.1016/j.jmb.2018.05.026
- ↑ Verba KA, Wang RY, Arakawa A, Liu Y, Shirouzu M, Yokoyama S, Agard DA. Atomic structure of Hsp90-Cdc37-Cdk4 reveals that Hsp90 traps and stabilizes an unfolded kinase. Science. 2016 Jun 24;352(6293):1542-7. doi: 10.1126/science.aaf5023. PMID:27339980 doi:http://dx.doi.org/10.1126/science.aaf5023
- ↑ Czemeres J, Buse K, Verkhivker GM. Atomistic simulations and network-based modeling of the Hsp90-Cdc37 chaperone binding with Cdk4 client protein: A mechanism of chaperoning kinase clients by exploiting weak spots of intrinsically dynamic kinase domains. PLoS One. 2017 Dec 21;12(12):e0190267. doi: 10.1371/journal.pone.0190267., eCollection 2017. PMID:29267381 doi:http://dx.doi.org/10.1371/journal.pone.0190267
