Sandbox Reserved 1767: Difference between revisions

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OCA, Jaime Prilusky, Kayla Wilhoite, Sloan August, Rosa Trippel, R. Jeremy Johnson

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 === PP1C ===
 [[Image:CS.png|300 px|right|thumb|'''Figure 2:''' Catalytic Site of PP1C (PDB 7DSO) <ref name="Liau">PMID: 35768504</ref>.]]
-<scene name='95/952695/Pp1cintro/3'>The Protein Phosphatase Complex 1 (PP1C)</scene> subunit contains the catalytic site of the SMP complex. PP1C is a [https://en.wikipedia.org/wiki/Phosphatase. 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 Mn⁺² and 1 Cl⁻¹ present that coordinate nucleophilic water molecules in the active site <ref name="Hauseman">PMID:35830882</ref>. This dephosphorylation event allows for pathway activation <ref name="Liau">PMID: 35768504</ref>. 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. 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 as shown in '''Figure 2''' in red.
+<scene name='95/952695/Pp1cintro/3'>The Protein Phosphatase Complex 1 (PP1C)</scene> subunit contains the catalytic site of the SMP complex. PP1C is a [https://pubmed.ncbi.nlm.nih.gov/30036567/. 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 Mn⁺² and 1 Cl⁻¹ present that coordinate nucleophilic water molecules in the active site <ref name="Hauseman">PMID:35830882</ref>. This dephosphorylation event allows for pathway activation <ref name="Liau">PMID: 35768504</ref>. 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. 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 as shown in '''Figure 2''' in red.
 PP1C binds to SHOC2 through a hydrophobic N-terminal disordered region that is complimentary to the <scene name='95/952695/Rvxf_motif/2'>RVXF Motif on SHOC2</scene> and adjacent to a catalytic metal ions <ref name="Liau">PMID: 35768504</ref>.  In the RAS/RAF signaling cascade, the region of RAF that is C-terminal to the phosphate group binds to this hydrophobic groove, and the remaining residues bind to the hydrophobic region of SHOC2 <ref name="Hauseman">PMID:35830882</ref>. RAF binding to this region of SHOC2 is what allows PP1C to be specific when in the SMP complex in comparison to PP1C on its own <ref name="Hauseman">PMID:35830882</ref>. Similarly to SHOC2, PP1C does not undergo a <scene name='95/952694/Pp1coverlay/4'>significant conformational change</scene> when SHOC2 and MRAS-GTP bind. The lack of conformational change shows that the structure of PP1C is not dependent on the SMP complex, but in order to act as a phosphatase it must be bound to the complex <ref name="Liau">PMID: 35768504</ref>.