Sandbox Reserved 1766

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<scene name='95/952694/Shoc2_pp1c_loops/1'>SHOC2 PP1C MRas</scene>{{Template:CH462_Biochemistry_II_2023}}<!-- PLEASE ADD YOUR CONTENT BELOW HERE -->
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<scene name='95/952694/Cell_membrane_mras_attachment/1'>Text To Be Displayed</scene><scene name='95/952694/Shoc2_pp1c_loops/1'>SHOC2 PP1C MRas</scene>{{Template:CH462_Biochemistry_II_2023}}<!-- PLEASE ADD YOUR CONTENT BELOW HERE -->
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==Your Heading Here (maybe something like 'Structure')==
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==Structure==
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene='95/952694/Overall_image/1'>
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene='95/952694/Overall_image/1'>
This is a default text for your page ''''''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.
This is a default text for your page ''''''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.
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<scene name='95/952694/Shoc2_pp1c_loops/1'>SHOC2 and PP1C Interface</scene>
<scene name='95/952694/Shoc2_pp1c_loops/1'>SHOC2 and PP1C Interface</scene>
=== MRAS ===
=== MRAS ===
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<scene name='95/952694/Cell_membrane_mras_attachment/1'>Cell Membrane Bound RAS Model</scene>
=== Binding of the Subunits ===
=== Binding of the Subunits ===
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== Structure of Active Site ==
== Structure of Active Site ==
=== 3-Metal Ion Catalysis ===
=== 3-Metal Ion Catalysis ===
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The <scene name='95/952695/Pp1c_active_site/3'>Catalytic Active Site</scene> of the SHOC2-PP1C-MRAS complex resides in the PP1C subunit. The role of PP1C is to dephosphorylate SER259 of Raf so that the signaling cascade can start. The active site is unchanged upon the binding of the complex, however, SHOC2 and MRAS aid in the specificity of the enzymatic activity as PP1C is able to dephosphorylate many different targets on its own, with almost 100 PP1C targets found. The full mechanism for the catalytic activity is unknown, however, there are 3 metal ions present (2-Mg2+ and 1-Cl-) to stabilize the waters present in the active site. Additionally, the substrate binds through hydrogen bonds with the main chain and side chain atoms of the catalytic residues. Mutations in the active site lead to increased activity, causing the Ras/Raf signaling cascade to be triggered more frequently.
 
=== Hydrophobic Binding Site ===
=== Hydrophobic Binding Site ===
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PP1C has a <scene name='95/952695/Hydrophobic_bindning_site/3'>TextToBeDisplayed</scene> adjacent to its active site. The majority of PP1C targets are able to bind through a specific motif that is recognized by the hydrophobic groove. In the Ras/Raf signaling cascade, the region of Raf that is C-terminal to the phosphate group binds to the hydrophobic groove, and the remaining residues bind to the hydrophobic region of SHOC2. This binding to SHOC2 is what allows the SMP complex to be more specific than PP1C on its own.
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== Future Directions ==
== Future Directions ==

Revision as of 04:07, 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.
To get started:
  • Click the edit this page tab at the top. Save the page after each step, then edit it again.
  • show the Scene authoring tools, create a molecular scene, and save it. Copy the green link into the page.
  • Add a description of your scene. Use the buttons above the wikitext box for bold, italics, links, headlines, etc.

More help: Help:Editing

Structure

Caption for this structure

Drag the structure with the mouse to rotate

References


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].

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