Sandbox Reserved 1706: Difference between revisions

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Neurofibromin is a [https://en.wikipedia.org/wiki/Protein_dimer protein dimer] that exists in the<scene name='90/904311/Closed_conformation/3'>closed</scene> and <scene name='90/904311/Open_conformation/2'>open</scene> conformation. Each [https://en.wikipedia.org/wiki/Protomer protomer] contains a GRD, Sec14-PH, and a GAPex domain located on a HEAT N-C arm. Ras binds to the GRD site with Arg1276 being the critical residue for binding.

===Closed conformation===

Ras is unable to bind to the GRD active site when both of the NF1 protomers are in the closed confirmation. In the<scene name='90/904311/Closed_conformation/4'>closed conformation</scene>, one protomer has its domains shifted by a 130 degree rotation of three separate linkers. That rotation places <scene name='90/904311/Closed_arg/3'>Arg1276 in the closed conformation</scene> in an orientation that <scene name='90/904312/Closed_zoom/1'>sterical hinders the binding between Ras and Arg1276</scene> in the GRD site (Figure 3). Also in this depiction Ras binding to the GRD site is inhibited by the N-HEAT ARM as it interferes at the GRD in Ras attempting to bind to the active site and is sterically hindered. Making <scene name='90/904312/Closed_with_ras/1'>Ras binding in closed conformation</scene> sterically impossible in the <scene name='90/904311/Closed_conformation/3'>closed conformation</scene>

Ras is unable to bind to the GRD active site when both of the NF1 protomers are in the closed confirmation. In the<scene name='90/904311/Closed_conformation/4'>closed conformation</scene>, one protomer has its domains shifted by a 130 degree rotation of three separate linkers. That rotation places <scene name='90/904311/Closed_arg/4'>Arg1276 in the closed conformation</scene> in an orientation that <scene name='90/904312/Closed_zoom/1'>sterical hinders the binding between Ras and Arg1276</scene> in the GRD site (Figure 3). Also in this depiction Ras binding to the GRD site is inhibited by the N-HEAT ARM as it interferes at the GRD in Ras attempting to bind to the active site and is sterically hindered. Making <scene name='90/904312/Closed_with_ras/1'>Ras binding in closed conformation</scene> sterically impossible in the <scene name='90/904311/Closed_conformation/3'>closed conformation</scene>

. The <scene name='90/904311/Closed_conformation/3'>closed conformation</scene> can exist naturally without any form of stabilization but will also fall back to the <scene name='90/904311/Open_conformation/2'>open conformation</scene>.

====Zinc Stabilized====

Sandbox Reserved 1706: Difference between revisions

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 Neurofibromin is a [https://en.wikipedia.org/wiki/Protein_dimer protein dimer] that exists in the<scene name='90/904311/Closed_conformation/3'>closed</scene> and <scene name='90/904311/Open_conformation/2'>open</scene> conformation. Each [https://en.wikipedia.org/wiki/Protomer protomer] contains a GRD, Sec14-PH, and a GAPex domain located on a HEAT N-C arm. Ras binds to the GRD site with Arg1276 being the critical residue for binding.
 ===Closed conformation===
-Ras is unable to bind to the GRD active site when both of the NF1 protomers are in the closed confirmation. In the<scene name='90/904311/Closed_conformation/4'>closed conformation</scene>, one protomer has its domains shifted by a 130 degree rotation of three separate linkers. That rotation places <scene name='90/904311/Closed_arg/3'>Arg1276 in the closed conformation</scene> in an orientation that <scene name='90/904312/Closed_zoom/1'>sterical hinders the binding between Ras and Arg1276</scene> in the GRD site (Figure 3). Also in this depiction Ras binding to the GRD site is inhibited by the N-HEAT ARM as it interferes at the GRD in Ras attempting to bind to the active site and is sterically hindered. Making <scene name='90/904312/Closed_with_ras/1'>Ras binding in closed conformation</scene> sterically impossible in the <scene name='90/904311/Closed_conformation/3'>closed conformation</scene>
+Ras is unable to bind to the GRD active site when both of the NF1 protomers are in the closed confirmation. In the<scene name='90/904311/Closed_conformation/4'>closed conformation</scene>, one protomer has its domains shifted by a 130 degree rotation of three separate linkers. That rotation places <scene name='90/904311/Closed_arg/4'>Arg1276 in the closed conformation</scene> in an orientation that <scene name='90/904312/Closed_zoom/1'>sterical hinders the binding between Ras and Arg1276</scene> in the GRD site (Figure 3). Also in this depiction Ras binding to the GRD site is inhibited by the N-HEAT ARM as it interferes at the GRD in Ras attempting to bind to the active site and is sterically hindered. Making <scene name='90/904312/Closed_with_ras/1'>Ras binding in closed conformation</scene> sterically impossible in the <scene name='90/904311/Closed_conformation/3'>closed conformation</scene>
 . The <scene name='90/904311/Closed_conformation/3'>closed conformation</scene> can exist naturally without any form of stabilization but will also fall back to the <scene name='90/904311/Open_conformation/2'>open conformation</scene>.
 ====Zinc Stabilized====