Sandbox Reserved 1767: Difference between revisions
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== Structure of Subunits == | == Structure of Subunits == | ||
=== SHOC2 === | === SHOC2 === | ||
The presence of <scene name='95/952695/Shoc2intro/1'>SHOC2</scene> is essential for complex formation. It a crescent shaped complex that serves as a bridge for PP1C and MRAS, maximizing interaction between the three subunits of the SMP complex. <ref name="Hauseman">PMID:35830882</ref>SHOC2 contains a large leucine rich region (LRR) that provides stability and localizes subunit PP1C to the membrane<ref name="Liau">PMID: 35768504</ref>. SHOC2 only undergoes a <scene name='95/952693/Shoc2_gtp_bound_vs_gdp_bound/7'>6° conformational change</scene> when PP1C and MRAS bind, showing SHOC2 is a scaffolding protein that provides a favorable interface for complex formation<ref name="Liau">PMID: 35768504</ref>. SHOC2 depletion is being studied as a therapeutic approach for RAS-driven cancers due to large scale interactions of the subunits being made possible by SHOC2. <ref name="Kwon">PMID: 35831509</ref>. SHOC2 and PP1C first engage in binding with each other via an N-terminal <scene name='95/952695/Rvxf_motif/2'>RVXF Motif</scene> on SHOC2 that is complimentary to a binding sequence on PP1C. SHOC2 residues <scene name='95/952695/Shoc2_highlighted_residues/1'>V64 and F66</scene> embed in the complimentary region of PP1C, enhancing SHOC2 affinity for PP1C. SHOC2 bind MRAS-GTP through β strands of a LRR that interacts with a hydrophobic region of MRAS-GTP further stabilizing the complex. | The presence of <scene name='95/952695/Shoc2intro/1'>SHOC2</scene> is essential for complex formation. It a crescent shaped complex that serves as a bridge for PP1C and MRAS, maximizing interaction between the three subunits of the SMP complex. <ref name="Hauseman">PMID:35830882</ref>SHOC2 contains a large leucine rich region (LRR) that provides stability and localizes subunit PP1C to the membrane<ref name="Liau">PMID: 35768504</ref>. SHOC2 only undergoes a <scene name='95/952693/Shoc2_gtp_bound_vs_gdp_bound/7'>6° conformational change</scene> when PP1C and MRAS bind, showing SHOC2 is a scaffolding protein that provides a favorable interface for complex formation<ref name="Liau">PMID: 35768504</ref>. SHOC2 depletion is being studied as a therapeutic approach for RAS-driven cancers due to large scale interactions of the subunits being made possible by SHOC2. <ref name="Kwon">PMID: 35831509</ref>. SHOC2 and PP1C first engage in binding with each other via an N-terminal <scene name='95/952695/Rvxf_motif/2'>RVXF Motif</scene> on SHOC2 that is complimentary to a binding sequence on PP1C. SHOC2 residues <scene name='95/952695/Shoc2_highlighted_residues/1'>V64 and F66</scene> embed in the complimentary region of PP1C, enhancing SHOC2 affinity for PP1C. SHOC2 bind MRAS-GTP through β strands of a LRR that interacts with a hydrophobic region of MRAS-GTP further stabilizing the complex.<ref name="Kwon">PMID: 35831509</ref> | ||
=== PP1C === | === PP1C === | ||
<scene name='95/952695/Pp1cintro/3'>The Protein Phosphatase Complex 1 (PP1C)</scene> subunit contains the catalytic site of the SMP complex. The PP1C subunit is a phosphatase enzyme responsible for the removal of a phosphate group on the N-terminal phosphoserine (NTpS) of RAF (Ser259).<ref name="Liau">PMID: 35768504</ref>. The exact mechanism of dephosphorylation is currently unknown, but there are three catalytic metal ions: 2 Mn2+ and 1 Cl- present that coordinate nucleophilic water molecules in the active site. This dephosphorylation event allows for pathway activation. Although PP1C can dephosphorylate other proteins independently from the SMP complex, it cannot act on Raf unless bound to the complex because it lacks intrinsic substrate selectivity.<ref name="Liau">PMID: 35768504</ref> SHOC2 and MRAS aid in the specificity of the enzymatic activity. '''Hence, PP1C requires the presence of SHOC2 and MRAS to be function.''' johnson said rewrite this sentence <ref name="Hauseman">PMID:35830882</ref> PP1C binds to SHOC2 and MRAS-GTP in a specific orientation that doesn’t change the conformation of the catalytic site and leaves it accessible for substrate binding.''' SHOW IN 2D SURFACE IMAGE''' | <scene name='95/952695/Pp1cintro/3'>The Protein Phosphatase Complex 1 (PP1C)</scene> subunit contains the catalytic site of the SMP complex. The PP1C subunit is a phosphatase enzyme responsible for the removal of a phosphate group on the N-terminal phosphoserine (NTpS) of RAF (Ser259).<ref name="Liau">PMID: 35768504</ref>. The exact mechanism of dephosphorylation is currently unknown, but there are three catalytic metal ions: 2 Mn2+ and 1 Cl- present that coordinate nucleophilic water molecules in the active site. This dephosphorylation event allows for pathway activation. Although PP1C can dephosphorylate other proteins independently from the SMP complex, it cannot act on Raf unless bound to the complex because it lacks intrinsic substrate selectivity.<ref name="Liau">PMID: 35768504</ref> SHOC2 and MRAS aid in the specificity of the enzymatic activity. '''Hence, PP1C requires the presence of SHOC2 and MRAS to be function.''' johnson said rewrite this sentence <ref name="Hauseman">PMID:35830882</ref> PP1C binds to SHOC2 and MRAS-GTP in a specific orientation that doesn’t change the conformation of the catalytic site and leaves it accessible for substrate binding.''' SHOW IN 2D SURFACE IMAGE''' | ||
