Sandbox Reserved 1706: Difference between revisions

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==Ras Binding==
==Ras Binding==
Arg1276 is the critical residue within the GRD site for Ras activation.  In the open conformation, the arginine finger binds to the backbone γ-carbon of Y32 in Ras to assist in eventual hydrolysis of GTP. In the closed conformation, this interaction between Y32 and GTP is blocked by E31. Removal of the inhibition of E31 from Ras by R1276 from Neurofibromin allows for the normal function of neurofibromin in the rapid rate increase of GTP hydrolysis upon Ras binding. Mutations to the arginine finger slow GTPase activating reaction of neurofibromin.<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>  
Arg1276 is the critical residue within the GRD site for Ras activation.  In the open conformation, the arginine finger binds to the backbone γ-carbon of Y32 in Ras to assist in eventual hydrolysis of GTP. In the closed conformation, this interaction between Y32 and GTP is blocked by E31. Removal of the inhibition of E31 from Ras by R1276 from Neurofibromin allows for the normal function of neurofibromin in the rapid rate increase of GTP hydrolysis upon Ras binding. Mutations to the arginine finger slow GTPase activating reaction of neurofibromin.<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|400px|left|thumb| Figure 3: Arg1276 of the GRD active site is sterically hindered in the closed conformation by Glu31 of Ras as it attempts to interact with the γ-carbon of Tyr32, but is unable to properly form a bond. Making binding to Ras impossible in the closed conformation. ]] [[Image:OpenArgFinger.PNG|400px|none|thumb|Figure 4: Arg1276 of the GRD active site is no longer sterically hindered in the open conformation by Glu31 of Ras, making it able to interact with γ-carbon of Tyr32 and form a bond with Ras.  ]]
==SPRED 1==
==SPRED 1==
SPRED 1 is another peripheral protein that interacts with the GRD domain of Neurofibromin. SPRED 1 recruits Neurofibromin from the cytosol to the plasma membrane to interact with Ras. Binding of SPRED 1 can occur in either the open or closed conformation and causes a structural rearrangement of the GRD domain and GAPex subdomain that has yet to be structuralized.<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 another peripheral protein that interacts with the GRD domain of Neurofibromin. SPRED 1 recruits Neurofibromin from the cytosol to the plasma membrane to interact with Ras. Binding of SPRED 1 can occur in either the open or closed conformation and causes a structural rearrangement of the GRD domain and GAPex subdomain that has yet to be structuralized.<ref name="Lupton"> DOI:10.1038/s41594-021-00687-2</ref><ref name="Naschberger"> DOI:10.1038/s41586-021-04024-x</ref>
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