Sandbox Reserved 1777: Difference between revisions

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==Active Site of PP1C==

Once all the domains are bound, [https://en.wikipedia.org/wiki/Nucleoside_triphosphate NTpS] binds to ~~PP1C in~~ the active site. NTpS refers to the phosphorylated serine (residue 259) located at the N-terminus of RAF. Once NTpS is bound, PP1C catalyzes the dephosphorylation of serine 259. NTpS is dephosphorylated to prevent the active dimeric RAF from inactivating and changing into its monomeric structure. Notably, NTpS can bind to the PP1C active site without PP1C being in complex with SHOC2 and MRAS. This occurs when RAS binds to RAF, which exposes NTpS on RAF. However, for this reaction, the catalytic activity of PP1C outside of the complex is less efficient. It's hypothesized this is because hydrophobic residues directly C-terminal to the phosphorylated serine bind to the hydrophobic patch of PP1C as well as the hydrophobic SHOC2 C-terminus<ref name="Liau">PMID:35768504</ref>. The conserved hydrophobic groove at the SHOC2 C-terminus and the hydrophobic region next to the PP1C active site neighbor each other in the structure of the complex. As a result, the hydrophobic residues downstream from NTpS bind to the hydrophobic path of PP1C next to the active site and to the hydrophobic groove in the SHOC2 C-terminus. '''<scene name='95/952705/Pp1c_active_site/4'>NTpS</scene> is surrounded by hydrophobic and acidic regions in the C-terminal direction. Similarly, hydrophobic regions are located on the surface of PP1C, whereas the active site is placed further into the structure of PP1C due to its charged nature. It is thought that these regions help NTpS bind to the active site by making interactions that will lead NTpS into the protein. There is still some uncertainty as to how the substrate selectivity works, but these regions could play an essential role in it.<ref name="Liau">PMID:35768504</ref>.'''

Once all the domains are bound, [https://en.wikipedia.org/wiki/Nucleoside_triphosphate NTpS] binds to the <scene name='95/952705/Pp1c_active_site/6'>active site of PP1C</scene>. NTpS refers to the phosphorylated serine (residue 259) located at the N-terminus of RAF. Once NTpS is bound, PP1C catalyzes the dephosphorylation of serine 259. NTpS is dephosphorylated to prevent the active dimeric RAF from inactivating and changing into its monomeric structure.

'''NTpS can bind to the PP1C active site without PP1C also being bound to SHOC2 and MRAS, however, the catalytic activity is much slower and the reaction is less efficient. In order for NTpS to bind PP1C in the absence of the other two proteins, NTpS would need to be exposed from its binding site in the inactive RAF complex. RAS has to bind to RAF to expose the NTpS, allowing PP1C and NTpS to bind.'''

~~<scene name='95/952705/Pp1c_active_site/5'>TextToBeDisplayed</scene> '''let me know thought on the style of image'''~~

<~~scene~~ name=~~'95/952705/Pp1c_active_site/6'~~>~~PP1C Active Site~~</~~scene~~>

Notably, NTpS can bind to the PP1C active site without PP1C being in complex with SHOC2 and MRAS. This occurs when RAS binds to RAF, which exposes NTpS on RAF. However, for this reaction, the catalytic activity of PP1C outside of the complex is less efficient. It's hypothesized this is because hydrophobic residues directly C-terminal to the phosphorylated serine bind to the hydrophobic patch of PP1C as well as the hydrophobic SHOC2 C-terminus<ref name="Liau">PMID:35768504</ref>.

The conserved hydrophobic groove at the SHOC2 C-terminus and the hydrophobic region next to the PP1C active site neighbor each other in the structure of the complex. As a result, the hydrophobic residues downstream from NTpS bind to the hydrophobic patch of PP1C next to the active site and to the hydrophobic groove in the SHOC2 C-terminus. '''<scene name='95/952705/Pp1c_active_site/4'>NTpS</scene> is surrounded by hydrophobic and acidic regions in the C-terminal direction. Similarly, hydrophobic regions are located on the surface of PP1C, whereas the active site is placed further into the structure of PP1C due to its charged nature. It is thought that these regions help NTpS bind to the active site by making interactions that will lead NTpS into the protein. There is still some uncertainty as to how the substrate selectivity works, but these regions could play an essential role in it.<ref name="Liau">PMID:35768504</ref>.'''

=Activation of RAF=

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 ==Active Site of PP1C==
-Once all the domains are bound, [https://en.wikipedia.org/wiki/Nucleoside_triphosphate NTpS] binds to PP1C in the active site. NTpS refers to the phosphorylated serine (residue 259) located at the N-terminus of RAF. Once NTpS is bound, PP1C catalyzes the dephosphorylation of serine 259. NTpS is dephosphorylated to prevent the active dimeric RAF from inactivating and changing into its monomeric structure. Notably, NTpS can bind to the PP1C active site without PP1C being in complex with SHOC2 and MRAS. This occurs when RAS binds to RAF, which exposes NTpS on RAF. However, for this reaction, the catalytic activity of PP1C outside of the complex is less efficient. It's hypothesized this is because hydrophobic residues directly C-terminal to the phosphorylated serine bind to the hydrophobic patch of PP1C as well as the hydrophobic SHOC2 C-terminus<ref name="Liau">PMID:35768504</ref>. The conserved hydrophobic groove at the SHOC2 C-terminus and the hydrophobic region next to the PP1C active site neighbor each other in the structure of the complex. As a result, the hydrophobic residues downstream from NTpS bind to the hydrophobic path of PP1C next to the active site and to the hydrophobic groove in the SHOC2 C-terminus. '''<scene name='95/952705/Pp1c_active_site/4'>NTpS</scene> is surrounded by hydrophobic and acidic regions in the C-terminal direction. Similarly, hydrophobic regions are located on the surface of PP1C, whereas the active site is placed further into the structure of PP1C due to its charged nature. It is thought that these regions help NTpS bind to the active site by making interactions that will lead NTpS into the protein. There is still some uncertainty as to how the substrate selectivity works, but these regions could play an essential role in it.<ref name="Liau">PMID:35768504</ref>.'''
+Once all the domains are bound, [https://en.wikipedia.org/wiki/Nucleoside_triphosphate NTpS] binds to the <scene name='95/952705/Pp1c_active_site/6'>active site of PP1C</scene>. NTpS refers to the phosphorylated serine (residue 259) located at the N-terminus of RAF. Once NTpS is bound, PP1C catalyzes the dephosphorylation of serine 259. NTpS is dephosphorylated to prevent the active dimeric RAF from inactivating and changing into its monomeric structure.
-'''NTpS can bind to the PP1C active site without PP1C also being bound to SHOC2 and MRAS, however, the catalytic activity is much slower and the reaction is less efficient. In order for NTpS to bind PP1C in the absence of the other two proteins, NTpS would need to be exposed from its binding site in the inactive RAF complex. RAS has to bind to RAF to expose the NTpS, allowing PP1C and NTpS to bind.'''
-<scene name='95/952705/Pp1c_active_site/5'>TextToBeDisplayed</scene> '''let me know thought on the style of image'''
-<scene name='95/952705/Pp1c_active_site/6'>PP1C Active Site</scene>
+Notably, NTpS can bind to the PP1C active site without PP1C being in complex with SHOC2 and MRAS. This occurs when RAS binds to RAF, which exposes NTpS on RAF. However, for this reaction, the catalytic activity of PP1C outside of the complex is less efficient. It's hypothesized this is because hydrophobic residues directly C-terminal to the phosphorylated serine bind to the hydrophobic patch of PP1C as well as the hydrophobic SHOC2 C-terminus<ref name="Liau">PMID:35768504</ref>.
+The conserved hydrophobic groove at the SHOC2 C-terminus and the hydrophobic region next to the PP1C active site neighbor each other in the structure of the complex. As a result, the hydrophobic residues downstream from NTpS bind to the hydrophobic patch of PP1C next to the active site and to the hydrophobic groove in the SHOC2 C-terminus. '''<scene name='95/952705/Pp1c_active_site/4'>NTpS</scene> is surrounded by hydrophobic and acidic regions in the C-terminal direction. Similarly, hydrophobic regions are located on the surface of PP1C, whereas the active site is placed further into the structure of PP1C due to its charged nature. It is thought that these regions help NTpS bind to the active site by making interactions that will lead NTpS into the protein. There is still some uncertainty as to how the substrate selectivity works, but these regions could play an essential role in it.<ref name="Liau">PMID:35768504</ref>.'''
 =Activation of RAF=