Sandbox Reserved 1706: Difference between revisions
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<scene name='90/904311/Closed_arg/4'>Arg1276 in closed conformation </scene> | <scene name='90/904311/Closed_arg/4'>Arg1276 in closed conformation </scene> | ||
<scene name='90/904312/Closed_zoom/1'>(zoomed in)</scene> has steric clashing with Ras making binding of Ras impossible (Figure #). In the closed confirmation the Arginine finger attempts to bind the backbone gamma carbon(RAS) of a Tyrosine residue(Y32) to assist in hydrolysis, but instead clashes with a Glutamate residue(E31) that would otherwise not interfere in the open conformation and can no longer bind properly. This residue impacts binding of Ras and is of critical importance in determining if Ras is able to bind to the GRD site or not to assist in eventual hydrolysis of GTP. | <scene name='90/904312/Closed_zoom/1'>(zoomed in)</scene> has steric clashing with Ras making binding of Ras impossible (Figure #). In the closed confirmation the Arginine finger attempts to bind the backbone gamma carbon(RAS) of a Tyrosine residue(Y32) to assist in hydrolysis, but instead clashes with a Glutamate residue(E31) that would otherwise not interfere in the open conformation and can no longer bind properly. This residue impacts binding of Ras and is of critical importance in determining if Ras is able to bind to the GRD site or not to assist in eventual hydrolysis of GTP. | ||
Mutations to the arginine finger are shown to slow function of NF1 and other GTPases in their function in accelerating GTP hydrolysis. When a Ras GAP such as NF1 can functionally utilize its arginine finger, it allows NF1 to rapidly hydrolyze GTP when bound to Ras. This emphasizes the importance of the R1276 residue for the GRD site binding to Ras.<ref name="Bourne"> DOI:10.1038/39470</ref><ref name="Lupton"> DOI:10.1038/s41594-021-00687-2</ref><ref name="Naschberger"> DOI:10.1038/s41586-021-04024-x</ref> | Mutations to the arginine finger are shown to slow function of NF1 and other GTPases in their function in accelerating GTP hydrolysis. When a Ras GAP such as NF1 can functionally utilize its arginine finger, it allows NF1 to rapidly hydrolyze GTP when bound to Ras. This emphasizes the importance of the R1276 residue for the GRD site binding to Ras.<ref name="Bourne"> DOI:10.1038/39470</ref><ref name="Lupton"> DOI:10.1038/s41594-021-00687-2</ref><ref name="Naschberger"> DOI:10.1038/s41586-021-04024-x</ref> [[Image:ClosedArgFinger.PNG|300px|left|thumb| blah]] [[Image:OpenArgFinger.PNG|300px|right|thumb|blah]] | ||
==SPRED 1== | ==SPRED 1== | ||
SPRED 1 is a protein that binds to the GAPex domain of Neurofibromin. Its function recruits the Neurofibromin protein when bound from the cytosol to the plasma membrane. SPRED 1 will bind to the GAPex domain of Neurofibromin in the <scene name='90/904311/Sped-1_closed/1'>closed conformation'</scene> in the cytosol to recruit Neurofibromin to the plasma membrane. Unlike Ras, SPRED-1 does show the ability to <scene name='90/904311/Spred-1_open/1'>bind to the open conformation</scene>. When bound to the open conformation of Neurofibromin in the cytosol, it may present a different orientation that impacts the recruitment to the plasma membrane. Further research is needed to assess the impact of the function and the changes it may present.<ref name="Lupton"> DOI:10.1038/s41594-021-00687-2</ref><ref name="Naschberger"> DOI:10.1038/s41586-021-04024-x</ref> | SPRED 1 is a protein that binds to the GAPex domain of Neurofibromin. Its function recruits the Neurofibromin protein when bound from the cytosol to the plasma membrane. SPRED 1 will bind to the GAPex domain of Neurofibromin in the <scene name='90/904311/Sped-1_closed/1'>closed conformation'</scene> in the cytosol to recruit Neurofibromin to the plasma membrane. Unlike Ras, SPRED-1 does show the ability to <scene name='90/904311/Spred-1_open/1'>bind to the open conformation</scene>. When bound to the open conformation of Neurofibromin in the cytosol, it may present a different orientation that impacts the recruitment to the plasma membrane. Further research is needed to assess the impact of the function and the changes it may present.<ref name="Lupton"> DOI:10.1038/s41594-021-00687-2</ref><ref name="Naschberger"> DOI:10.1038/s41586-021-04024-x</ref> | ||
