Sandbox Reserved 1790: Difference between revisions
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===SHOC2 and MRAS interactions=== | ===SHOC2 and MRAS interactions=== | ||
[[Image:Freak2.png|500 px|thumb|'''Figure 1:'''Steric clashing of Switch I and II of GDP bound MRAS (green) with the surface of SHOC2 (magenta). GTP-bound MRAS (white) removes steric clashing with SHOC2 allowing tight binding between GTP-MRAS and SHOC2.[https://www.rcsb.org/structure/7UPI. | [[Image:Freak2.png|500 px|thumb|'''Figure 1:'''Steric clashing of Switch I and II of GDP bound MRAS (green) with the surface of SHOC2 (magenta). GTP-bound MRAS (white) removes steric clashing with SHOC2 allowing tight binding between GTP-MRAS and SHOC2.[https://www.rcsb.org/structure/7UPI. '7UPI']</div></font>]] | ||
MRAS is initially bound to GDP causing it to be in its inactive state. Inactive GDP-MRAS cannot bind to the SHOC2-PP1C complex due to steric clashing of the switch I and II regions of MRAS and its binding zone on SHOC2. Once GDP is exchanged for GTP when signaled by growth factors, MRAS is activated and conformational changes occur within the switch I and switch II regions to allow <scene name='95/952716/Newmras-shco2/10'>MRAS to interact with SHOC2</scene>. These <scene name='95/952716/Scho2-mras-interactions/1'>interactions</scene> between SHOC2 and the switch I and II regions of MRAS include hydrogen bonds, ionic interactions, and π stacking. There is a hydrogen bond at R288-Q71 and ionic interaction at R177-E47. π staking occurs at R104-R83. These interactions occur between SHOC2 and MRAS respectively <ref name="Lavoie">Lavoie H, Therrien M. Structural keys unlock RAS-MAPK cellular signaling pathway. Nature. 2022 Sep;609(7926):248-249. [http://dx.doi.org/10.1038/d41586-022-02189-7 doi: 10.1038/d41586-022-02189-7. PMID: 35970881.]</ref>. | MRAS is initially bound to GDP causing it to be in its inactive state. Inactive GDP-MRAS cannot bind to the SHOC2-PP1C complex due to steric clashing of the switch I and II regions of MRAS and its binding zone on SHOC2. Once GDP is exchanged for GTP when signaled by growth factors, MRAS is activated and conformational changes occur within the switch I and switch II regions to allow <scene name='95/952716/Newmras-shco2/10'>MRAS to interact with SHOC2</scene>. These <scene name='95/952716/Scho2-mras-interactions/1'>interactions</scene> between SHOC2 and the switch I and II regions of MRAS include hydrogen bonds, ionic interactions, and π stacking. There is a hydrogen bond at R288-Q71 and ionic interaction at R177-E47. π staking occurs at R104-R83. These interactions occur between SHOC2 and MRAS respectively <ref name="Lavoie">Lavoie H, Therrien M. Structural keys unlock RAS-MAPK cellular signaling pathway. Nature. 2022 Sep;609(7926):248-249. [http://dx.doi.org/10.1038/d41586-022-02189-7 doi: 10.1038/d41586-022-02189-7. PMID: 35970881.]</ref>. | ||