Sandbox Reserved 1710: Difference between revisions
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[[Image:Neurofibromin Surface w Labels.jpg|500 px|right|thumb|Figure 1: Surface Rendering of Neurofibromin in its Open (7PGT) and Closed (7PGR) Conformation.]] | [[Image:Neurofibromin Surface w Labels.jpg|500 px|right|thumb|Figure 1: Surface Rendering of Neurofibromin in its Open (7PGT) and Closed (7PGR) Conformation.]] | ||
Neurofibromin is encoded by [https://en.wikipedia.org/wiki/Neurofibromin_1 NF1 gene], located on chromosome 17. Neurofibromin functions as a tumor suppressor through its association with the protein [https://proteopedia.org/wiki/index.php/Ras Ras]. The molecular structure of Neurofibromin has been determined by [https://en.wikipedia.org/wiki/Cryogenic_electron_microscopy Cryo-Electron Microscopy]. The structure of neurofibromin isoform 2 revealed different functional states for the Neurofibromin protein.<ref name="Naschberger">PMID:34707296</ref> Mutations in Neurofibromin are associated with diseases such as [https://en.wikipedia.org/wiki/Neurofibroma Plexiform Neurofibromas]. (FLESH OUT INTRODUCTION) | Neurofibromin is encoded by [https://en.wikipedia.org/wiki/Neurofibromin_1 NF1 gene], located on chromosome 17. Neurofibromin functions as a tumor suppressor through its association with the protein [https://proteopedia.org/wiki/index.php/Ras Ras]. The molecular structure of Neurofibromin has been determined by [https://en.wikipedia.org/wiki/Cryogenic_electron_microscopy Cryo-Electron Microscopy]. The structure of neurofibromin isoform 2 revealed different functional states for the Neurofibromin protein.<ref name="Naschberger">PMID:34707296</ref> Mutations in Neurofibromin are associated with diseases such as [https://en.wikipedia.org/wiki/Neurofibroma Plexiform Neurofibromas]. (FLESH OUT INTRODUCTION) | ||
== Function == | == Function == | ||
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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/ | 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/4'>triad</scene> consisting of residues Cys 1032, His 1558, and His 1576 that form a transition metal-binding site with zinc. The rigid organization of the <scene name='90/904315/Catalytic_triade/4'>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 associating with Ras. In its active form, Ras and Neurofibromin will associate via an <scene name='90/904316/Arg_finger/2'>Arginine finger</scene> (Arg 1276). However, the steric hindrance 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. | ||
=== Open Conformation === | === Open Conformation === | ||
