Sandbox Reserved 1710: Difference between revisions
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=== Closed Conformation === | === Closed Conformation === | ||
In the <scene name='90/904315/Closed/3'>closed, inactive conformation</scene>, the GRD and Sec14-PH domains are rotated so Ras cannot bind. In this conformation, the GRD and Sec14-PH are inaccessible and inactive. Neurofibromin is held in the inactive state by a <scene name='90/904315/Closed_triade/7'>triad</scene> consisting of residues Cys1032, His1558, and His1576 that form a transition metal-binding site with zinc. The rigid organization of the <scene name='90/904315/Closed_triade/8'>triad in closed conformation</scene> keeps the GRD domain packed tightly on top of the Heat Arms in the Neurofibromin core. This tight compaction sterically occludes Neurofibromin from <scene name='90/904315/Closed_with_ras/2'>associating with Ras.</scene> In its active form, Ras and Neurofibromin will associate via an <scene name='90/904315/Arg_finger/5'>Arginine Finger</scene>(Arg1276). However, the <scene name='90/904315/Arg_finger/3'>steric hindrance</scene> from the Neurofibromin core in the closed conformation inhibits this association. Therefore, in the closed conformation, neurofibromin cannot catalyze GTP hydrolysis by Ras and Ras continues to signal for cell growth and proliferation.<ref name="Naschberger">PMID:34707296</ref> | In the <scene name='90/904315/Closed/3'>closed, inactive conformation</scene>, the GRD and Sec14-PH domains are rotated so Ras cannot bind. In this conformation, the GRD and Sec14-PH are inaccessible and inactive. Neurofibromin is held in the inactive state by a <scene name='90/904315/Closed_triade/7'>triad</scene> consisting of residues Cys1032, His1558, and His1576 that form a transition metal-binding site with zinc. The rigid organization of the <scene name='90/904315/Closed_triade/8'>triad in closed conformation</scene> keeps the GRD domain packed tightly on top of the Heat Arms in the Neurofibromin core. This tight compaction sterically occludes Neurofibromin from <scene name='90/904315/Closed_with_ras/2'>associating with Ras.</scene> In its active form, Ras and Neurofibromin will associate via an <scene name='90/904315/Arg_finger/5'>Arginine Finger</scene> (Arg1276). However, the <scene name='90/904315/Arg_finger/3'>steric hindrance</scene> from the Neurofibromin core in the closed conformation inhibits this association. Therefore, in the closed conformation, neurofibromin cannot catalyze GTP hydrolysis by Ras and Ras continues to signal for cell growth and proliferation.<ref name="Naschberger">PMID:34707296</ref> | ||
=== Open Conformation === | === Open Conformation === | ||
