Sandbox Reserved 1767: Difference between revisions
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== Structure of Subunits == | == Structure of Subunits == | ||
=== SHOC2 === | === SHOC2 === | ||
<scene name='95/952695/Shoc2intro/1'>SHOC2</scene> is essential for complex formation. It is 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/ | <scene name='95/952695/Shoc2intro/1'>SHOC2</scene> is essential for complex formation. It is 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='95/952695/Shoc2_gtp_bound_vs_gdp_bound/1'>6° conformational change</scene> when PP1C and MRAS bind showing it 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>. As shown in '''Figure 1 '''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 binds MRAS-GTP through β strands of a LRR that interacts with a [https://pubmed.ncbi.nlm.nih.gov/21954777/. hydrophobic] region of MRAS-GTP further stabilizing the complex<ref name="Kwon">PMID: 35831509</ref>. | ||
=== PP1C === | === PP1C === | ||
[[Image:CS.png|300 px|right|thumb|'''Figure 2:''' Catalytic Site of PP1C (PDB 7DSO). The catalytic site is shown in red. PP1C undergoes minimal conformational change when binding to SHOC2 and MRAS to ensure the active site is available for binding of RAF <ref name="Liau">PMID: 35768504</ref>.]] | [[Image:CS.png|300 px|right|thumb|'''Figure 2:''' Catalytic Site of PP1C (PDB 7DSO). The catalytic site is shown in red. PP1C undergoes minimal conformational change when binding to SHOC2 and MRAS to ensure the active site is available for binding of RAF <ref name="Liau">PMID: 35768504</ref>.]] | ||