Sandbox Reserved 1766
From Proteopedia
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| - | <scene name='95/952694/Overall_image/2'>SHOC2-PP1C-MRas Overall Structure</scene>{{Template:CH462_Biochemistry_II_2023}}<!-- PLEASE ADD YOUR CONTENT BELOW HERE --> | + | <scene name='95/952694/Mras_switch_i/3'>Text To Be Displayed</scene><scene name='95/952694/Overall_image/2'>SHOC2-PP1C-MRas Overall Structure</scene>{{Template:CH462_Biochemistry_II_2023}}<!-- PLEASE ADD YOUR CONTENT BELOW HERE --> |
==Structure== | ==Structure== | ||
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene='95/952694/Overall_image/2'> | <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene='95/952694/Overall_image/2'> | ||
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MRas localized the SHOC2 complex to the cell membrane by its C-terminus end. In its <scene name='95/952694/Cellmem2/1'>Cell Membrane Bound RAS Model</scene>, there is a modified chain that allows it to bind to the cell membrane.<ref name="Liau">PMID: 35768504</ref> Normally, MRas does not have the chain and it is only added after the modification. For MRas to bind, the SHOC-2 complex must be in the GTP bound state. When GDP is bound, there is a steric clash between Switch 1 and PP1C, so interaction with MRAS is not possible. Additionally, the surface of MRas that is buried in the complex overlaps the surfaces used to engage RAF. It requires two MRas interactions to activate a single RAF molecule. | MRas localized the SHOC2 complex to the cell membrane by its C-terminus end. In its <scene name='95/952694/Cellmem2/1'>Cell Membrane Bound RAS Model</scene>, there is a modified chain that allows it to bind to the cell membrane.<ref name="Liau">PMID: 35768504</ref> Normally, MRas does not have the chain and it is only added after the modification. For MRas to bind, the SHOC-2 complex must be in the GTP bound state. When GDP is bound, there is a steric clash between Switch 1 and PP1C, so interaction with MRAS is not possible. Additionally, the surface of MRas that is buried in the complex overlaps the surfaces used to engage RAF. It requires two MRas interactions to activate a single RAF molecule. | ||
| - | + | <scene name='95/952694/Mras_switch_i/3'>MRAS SWI </scene> | |
=== Binding of the Subunits === | === Binding of the Subunits === | ||
Revision as of 18:03, 3 April 2023
| This Sandbox is Reserved from February 27 through August 31, 2023 for use in the course CH462 Biochemistry II taught by R. Jeremy Johnson at the Butler University, Indianapolis, USA. This reservation includes Sandbox Reserved 1765 through Sandbox Reserved 1795. |
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Structure
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References
- ↑ 1.0 1.1 1.2 Liau NPD, Johnson MC, Izadi S, Gerosa L, Hammel M, Bruning JM, Wendorff TJ, Phung W, Hymowitz SG, Sudhamsu J. Structural basis for SHOC2 modulation of RAS signalling. Nature. 2022 Jun 29. pii: 10.1038/s41586-022-04838-3. doi:, 10.1038/s41586-022-04838-3. PMID:35768504 doi:http://dx.doi.org/10.1038/s41586-022-04838-3
1. Hauseman ZJ, Fodor M, Dhembi A, Viscomi J, Egli D, Bleu M, Katz S, Park E, Jang DM, Porter KA, Meili F, Guo H, Kerr G, Mollé S, Velez-Vega C, Beyer KS, Galli GG, Maira SM, Stams T, Clark K, Eck MJ, Tordella L, Thoma CR, King DA. Structure of the MRAS-SHOC2-PP1C phosphatase complex. Nature. 2022 Sep;609(7926):416-423. doi: 10.1038/s41586-022-05086-1. Epub 2022 Jul 13. PMID: 35830882; PMCID: PMC9452295.[1].
2. Hurley TD, Yang J, Zhang L, Goodwin KD, Zou Q, Cortese M, Dunker AK, DePaoli-Roach AA. Structural basis for regulation of protein phosphatase 1 by inhibitor-2. J Biol Chem. 2007 Sep 28;282(39):28874-28883. doi: 10.1074/jbc.M703472200. Epub 2007 Jul 18. PMID: 17636256.[2].
3. Kwon JJ, Hajian B, Bian Y, Young LC, Amor AJ, Fuller JR, Fraley CV, Sykes AM, So J, Pan J, Baker L, Lee SJ, Wheeler DB, Mayhew DL, Persky NS, Yang X, Root DE, Barsotti AM, Stamford AW, Perry CK, Burgin A, McCormick F, Lemke CT, Hahn WC, Aguirre AJ. Structure-function analysis of the SHOC2-MRAS-PP1C holophosphatase complex. Nature. 2022 Sep;609(7926):408-415. doi: 10.1038/s41586-022-04928-2. Epub 2022 Jul 13. PMID: 35831509; PMCID: PMC9694338.[3].
4. Liau NPD, Johnson MC, Izadi S, Gerosa L, Hammel M, Bruning JM, Wendorff TJ, Phung W, Hymowitz SG, Sudhamsu J. Structural basis for SHOC2 modulation of RAS signalling. Nature. 2022 Sep;609(7926):400-407. doi: 10.1038/s41586-022-04838-3. Epub 2022 Jun 29. PMID: 35768504; PMCID: PMC9452301.[4].
5. Lavoie H, Therrien M. Structural keys unlock RAS-MAPK cellular signalling pathway. Nature. 2022 Sep;609(7926):248-249. doi: 10.1038/d41586-022-02189-7. PMID: 35970881.[5].
6. Young LC, Hartig N, Boned Del Río I, Sari S, Ringham-Terry B, Wainwright JR, Jones GG, McCormick F, Rodriguez-Viciana P. SHOC2-MRAS-PP1 complex positively regulates RAF activity and contributes to Noonan syndrome pathogenesis. Proc Natl Acad Sci U S A. 2018 Nov 6;115(45):E10576-E10585. doi: 10.1073/pnas.1720352115. Epub 2018 Oct 22. PMID: 30348783; PMCID: PMC6233131.[6].
