Sandbox Reserved 1706: Difference between revisions
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===Open conformation=== | ===Open conformation=== | ||
In the <scene name='90/904311/Open_conformation/1'>open conformation</scene> one protomer is shifted due to a 90 rotation. This rotation allows for binding between RAS and the <scene name='90/904312/Arg_1276_open/10'>Arg1276</scene> | In the <scene name='90/904311/Open_conformation/1'>open conformation</scene> one protomer is shifted due to a 90 rotation. This rotation allows for binding between RAS and the <scene name='90/904312/Arg_1276_open/10'>Arg1276</scene> | ||
in the GRD site while in the <scene name='90/904311/Open_conformation/1'>open conformation</scene>. | in the GRD site while in the <scene name='90/904311/Open_conformation/1'>open conformation</scene>. Allowing for the <scene name='90/904312/Arg_1276_open/11'>Arg1276 interaction with Ras in the open conformation</scene> to occur without any steric hindrance as shown in the <scene name='90/904311/Closed_conformation/1'>closed conformation</scene>. | ||
===Conformational Change Linkers=== | ===Conformational Change Linkers=== | ||
The rotation of the domains between the <scene name='90/904311/Open_conformation/1'>open conformation</scene> and <scene name='90/904311/Closed_conformation/1'>closed conformation</scene> of NF1 are conducted by three helical linkers named L1, L2, and L3. The <scene name='90/904312/Linker_closed/1'>linkers in the closed conformation</scene> | |||
<scene name='90/904312/Linker_closed/2'>(zoomed in)'</scene> and the <scene name='90/904312/Linkers_open/2'>linkers in the open conformation</scene> | |||
<scene name='90/904312/Zoomed_lo/1'>(zoomed in)'</scene> undergo rotations to relocate the GRD and Sec14-PH sites. Linker 1 (L1) consists of a loop connected by two helices from L1173-M1215 and is the main contributor in rotation of the GRD domain. The rotation of L1 to the <scene name='90/904312/Linkers_open/2'>open conformation</scene> causes N-HEAT ARM alpha helix 48 and GRD helix 49 to extend out, aligning to form a hinge point at G1190. The GRD relocation is assisted by Sec14-PH relocation, which is initiated by Linker 3(L3) from Q1835 to G1852 where the proline rich section of the C-HEAT ARM changes conformation.L1 and L3 move closer to each other in the <scene name='90/904312/Linkers_open/2'>open conformation</scene>. Linker 2 (L2) consists of residues G1547-T1565 and begins at helix 63, the final helix of the GRD site, and connects into the short loop of alpha helix 65 of the Sec14-PH domain. The combination of these three linkers are responsible for the conformational shift of the <scene name='90/904312/Linker_closed/1'> closed conformation</scene> | |||
<scene name='90/904312/Linker_closed/2'>(zoomed in)'</scene> and <scene name='90/904312/Linkers_open/2'>open conformation</scene> | |||
<scene name='90/904312/Zoomed_lo/1'>(zoomed in)'</scene>. | |||
===Domains=== | ===Domains=== | ||
===Arginine 1276=== | ===Arginine 1276=== | ||
== | <scene name='90/904312/Arg_1276_open/10'>Arg1276 in open conformation</scene> | ||
<scene name='90/904312/Arg_1276_open/11'>Arg1276 interaction with Ras in open conformation</scene> | |||