Sandbox Reserved 1765: Difference between revisions
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<scene name='95/952693/Shoc2_gtp_bound_vs_gdp_bound/7'>Text To Be Displayed</scene>{{Template:CH462_Biochemistry_II_2023}}<!-- PLEASE ADD YOUR CONTENT BELOW HERE --> | |||
{{Template:CH462_Biochemistry_II_2023}}<!-- PLEASE ADD YOUR CONTENT BELOW HERE --> | |||
=SHOC2-PP1C-MRAS= | =SHOC2-PP1C-MRAS= | ||
<StructureSection load='1stp' size='340' side='right' caption='SHOC2-MRAS-PP1C Holophosphatase Complex' scene='95/952694/Overall_image/2'> | <StructureSection load='1stp' size='340' side='right' caption='SHOC2-MRAS-PP1C Holophosphatase Complex' scene='95/952694/Overall_image/2'> | ||
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In all images and animations, {{Font color|cyan|SHOC2}} will be shown as cyan blue, {{Font color|lime|MRAS}} as lime, and {{Font color|violet|PP1C}} as violet. Other important components involved in the function of the SMP complex include the {{Font color|salmon|14-3-3}} dimer and {{Font color|slate-blue|Raf}}, which will be shown in salmon and slate-blue, respectively. | In all images and animations, {{Font color|cyan|SHOC2}} will be shown as cyan blue, {{Font color|lime|MRAS}} as lime, and {{Font color|violet|PP1C}} as violet. Other important components involved in the function of the SMP complex include the {{Font color|salmon|14-3-3}} dimer and {{Font color|slate-blue|Raf}}, which will be shown in salmon and slate-blue, respectively. | ||
[[Image:RASRAF.png|250 px|right|thumb|Figure 2: MRAS binding sites with SHOC2, PP1C, and RAF (PDB 7DSO).<ref name="Liau">PMID: 35768504</ref>.]] | |||
<scene name='95/952693/Shoc2_gtp_bound_vs_gdp_bound/7'>6° conformational change</scene> | |||
== Structure of Subunits == | == Structure of Subunits == | ||
=== SHOC2 === | === SHOC2 === | ||
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The Ras-Raf signaling cascade will be inhibited without the dephosphorylation of Raf at Ser259. There is a <scene name='95/952695/14-3-3/1'>14-3-3</scene> dimer present in the cytoplasm that interacts with Raf through hydrogen bonds between R129 of 14-3-3 and Ser259 of Raf when Ser259 is phosphorylated. This interaction causes an <scene name='95/952695/Autoinhibited_confirmation/7'>autoinhibited confirmation</scene> as 14-3-3 restricts Raf to the cytoplasm and sterically inhibits Raf from binding with activated Ras. This interaction is crucial in regulating cell proliferation, as it prevents cell growth in the absence of a signal. Extracellular growth factors trigger GTP to bind to MRAS, which triggers SMP formation. Upon SMP complex formation, PP1C is brought into close proximity of Ras, leading to the dephosphorylation of Ser259 of Raf by the active site of PP1C. Once dephosphorylated, Raf is in the <scene name='95/952695/Non-inhibited_confirmation/9'>active confirmation</scene>, allowing for the interaction of Ras and Raf, and the initiation of the signaling cascade.<ref name="Young">PMID: 30348783</ref> | The Ras-Raf signaling cascade will be inhibited without the dephosphorylation of Raf at Ser259. There is a <scene name='95/952695/14-3-3/1'>14-3-3</scene> dimer present in the cytoplasm that interacts with Raf through hydrogen bonds between R129 of 14-3-3 and Ser259 of Raf when Ser259 is phosphorylated. This interaction causes an <scene name='95/952695/Autoinhibited_confirmation/7'>autoinhibited confirmation</scene> as 14-3-3 restricts Raf to the cytoplasm and sterically inhibits Raf from binding with activated Ras. This interaction is crucial in regulating cell proliferation, as it prevents cell growth in the absence of a signal. Extracellular growth factors trigger GTP to bind to MRAS, which triggers SMP formation. Upon SMP complex formation, PP1C is brought into close proximity of Ras, leading to the dephosphorylation of Ser259 of Raf by the active site of PP1C. Once dephosphorylated, Raf is in the <scene name='95/952695/Non-inhibited_confirmation/9'>active confirmation</scene>, allowing for the interaction of Ras and Raf, and the initiation of the signaling cascade.<ref name="Young">PMID: 30348783</ref> | ||
[[Image:pic3.jpg|250 px|right|thumb|Figure 2: MRAS binding sites with SHOC2, PP1C, and RAF (PDB 7DSO).<ref name="Liau">PMID: 35768504</ref>.]] | |||
=== Switch I and Switch II === | === Switch I and Switch II === | ||
