Sandbox Reserved 1710: Difference between revisions

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== Introduction ==

[[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 functions as a tumor suppressor protein by associating with [https://proteopedia.org/wiki/index.php/Ras Ras], a protein that ~~signals~~ [https://en.wikipedia.org/wiki/Cell_proliferation cell proliferation] and growth. It has two conformations, the open, active conformation and the closed, inactive conformation (Figure 1). <ref name="Trovó-Marqui">PMID:16813595</ref> The change in conformation of Neurofibromin from open to closed regulates Ras activity, turning it off, thus stopping cell growth from continuing in excess. Neurofibromin is a [https://en.wikipedia.org/wiki/Dimer_(chemistry) dimer] made up of two identical [https://en.wikipedia.org/wiki/Monomer monomers] consisting of the Sec 14-PH domain and the GRD (Gap-related domain). The orientation of these domains is important for the interaction and binding of Ras to the Arginine finger in Neurofibromin, a key interaction in the regulation of Ras activity. Neurofibromin in its open conformation allows for the Ras association, unlike the closed conformation which is unable to associate with Ras and turn it off. <ref name="Naschberger">PMID:34707296</ref> The closed conformation is stabilized by a triad consisting of Cys 1032, His 1558, and His 1576 and a Zinc atom. The molecular structure and detail of Neurofibromin have been determined by [https://en.wikipedia.org/wiki/Cryogenic_electron_microscopy Cryo-Electron Microscopy]. Additionally, the structure of Neurofibromin isoform 2 revealed different functional states for Neurofibromin. <ref name="Naschberger">PMID:34707296</ref> Neurofibromin is encoded by the [https://en.wikipedia.org/wiki/Neurofibromin_1 NF1 gene], which is located on chromosome 17. Mutations in the NF1 gene are associated with diseases including Neurofibromatosis Type 1, [https://en.wikipedia.org/wiki/Neurofibroma Plexiform Neurofibromas], and cancers including glioblastoma, neuroblastoma, lung, ovarian, and breast cancer. <ref name="Lupton">PMID: 34887559 </ref> <ref name="Ratner">PMID:25877329</ref> <ref name="Abramowicz">PMID:25182393</ref>

Neurofibromin functions as a tumor suppressor protein by associating with [https://proteopedia.org/wiki/index.php/Ras Ras], a protein that drives [https://en.wikipedia.org/wiki/Cell_proliferation cell proliferation] and growth. It has two conformations, the open, active conformation and the closed, inactive conformation (Figure 1). <ref name="Trovó-Marqui">PMID:16813595</ref> The change in conformation of Neurofibromin from open to closed regulates Ras activity, turning it off, thus stopping cell growth from continuing in excess. Neurofibromin is a [https://en.wikipedia.org/wiki/Dimer_(chemistry) dimer] made up of two identical [https://en.wikipedia.org/wiki/Monomer monomers] consisting of the Sec 14-PH domain and the GRD (Gap-related domain). The orientation of these domains is important for the interaction and binding of Ras to the Arginine finger in Neurofibromin, a key interaction in the regulation of Ras activity. Neurofibromin in its open conformation allows for the Ras association, unlike the closed conformation which is unable to associate with Ras and turn it off. <ref name="Naschberger">PMID:34707296</ref> The closed conformation is stabilized by a triad consisting of Cys 1032, His 1558, and His 1576 and a Zinc atom. The molecular structure and detail of Neurofibromin have been determined by [https://en.wikipedia.org/wiki/Cryogenic_electron_microscopy Cryo-Electron Microscopy]. Additionally, the structure of Neurofibromin isoform 2 revealed different functional states for Neurofibromin. <ref name="Naschberger">PMID:34707296</ref> Neurofibromin is encoded by the [https://en.wikipedia.org/wiki/Neurofibromin_1 NF1 gene], which is located on chromosome 17. Mutations in the NF1 gene are associated with diseases including Neurofibromatosis Type 1, [https://en.wikipedia.org/wiki/Neurofibroma Plexiform Neurofibromas], and cancers including glioblastoma, neuroblastoma, lung, ovarian, and breast cancer. <ref name="Lupton">PMID: 34887559 </ref> <ref name="Ratner">PMID:25877329</ref> <ref name="Abramowicz">PMID:25182393</ref>

== Function ==

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 == Introduction ==
 [[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 functions as a tumor suppressor protein by associating with [https://proteopedia.org/wiki/index.php/Ras Ras], a protein that signals [https://en.wikipedia.org/wiki/Cell_proliferation cell proliferation] and growth. It has two conformations, the open, active conformation and the closed, inactive conformation (Figure 1). <ref name="Trovó-Marqui">PMID:16813595</ref> The change in conformation of Neurofibromin from open to closed regulates Ras activity, turning it off, thus stopping cell growth from continuing in excess. Neurofibromin is a [https://en.wikipedia.org/wiki/Dimer_(chemistry) dimer] made up of two identical [https://en.wikipedia.org/wiki/Monomer monomers] consisting of the Sec 14-PH domain and the GRD (Gap-related domain). The orientation of these domains is important for the interaction and binding of Ras to the Arginine finger in Neurofibromin, a key interaction in the regulation of Ras activity. Neurofibromin in its open conformation allows for the Ras association, unlike the closed conformation which is unable to associate with Ras and turn it off. <ref name="Naschberger">PMID:34707296</ref> The closed conformation is stabilized by a triad consisting of Cys 1032, His 1558, and His 1576 and a Zinc atom. The molecular structure and detail of Neurofibromin have been determined by [https://en.wikipedia.org/wiki/Cryogenic_electron_microscopy Cryo-Electron Microscopy]. Additionally, the structure of Neurofibromin isoform 2 revealed different functional states for Neurofibromin. <ref name="Naschberger">PMID:34707296</ref> Neurofibromin is encoded by the [https://en.wikipedia.org/wiki/Neurofibromin_1 NF1 gene], which is located on chromosome 17. Mutations in the NF1 gene are associated with diseases including Neurofibromatosis Type 1, [https://en.wikipedia.org/wiki/Neurofibroma Plexiform Neurofibromas], and cancers including glioblastoma, neuroblastoma, lung, ovarian, and breast cancer. <ref name="Lupton">PMID: 34887559 </ref> <ref name="Ratner">PMID:25877329</ref> <ref name="Abramowicz">PMID:25182393</ref>
+Neurofibromin functions as a tumor suppressor protein by associating with [https://proteopedia.org/wiki/index.php/Ras Ras], a protein that drives [https://en.wikipedia.org/wiki/Cell_proliferation cell proliferation] and growth. It has two conformations, the open, active conformation and the closed, inactive conformation (Figure 1). <ref name="Trovó-Marqui">PMID:16813595</ref> The change in conformation of Neurofibromin from open to closed regulates Ras activity, turning it off, thus stopping cell growth from continuing in excess. Neurofibromin is a [https://en.wikipedia.org/wiki/Dimer_(chemistry) dimer] made up of two identical [https://en.wikipedia.org/wiki/Monomer monomers] consisting of the Sec 14-PH domain and the GRD (Gap-related domain). The orientation of these domains is important for the interaction and binding of Ras to the Arginine finger in Neurofibromin, a key interaction in the regulation of Ras activity. Neurofibromin in its open conformation allows for the Ras association, unlike the closed conformation which is unable to associate with Ras and turn it off. <ref name="Naschberger">PMID:34707296</ref> The closed conformation is stabilized by a triad consisting of Cys 1032, His 1558, and His 1576 and a Zinc atom. The molecular structure and detail of Neurofibromin have been determined by [https://en.wikipedia.org/wiki/Cryogenic_electron_microscopy Cryo-Electron Microscopy]. Additionally, the structure of Neurofibromin isoform 2 revealed different functional states for Neurofibromin. <ref name="Naschberger">PMID:34707296</ref> Neurofibromin is encoded by the [https://en.wikipedia.org/wiki/Neurofibromin_1 NF1 gene], which is located on chromosome 17. Mutations in the NF1 gene are associated with diseases including Neurofibromatosis Type 1, [https://en.wikipedia.org/wiki/Neurofibroma Plexiform Neurofibromas], and cancers including glioblastoma, neuroblastoma, lung, ovarian, and breast cancer. <ref name="Lupton">PMID: 34887559 </ref> <ref name="Ratner">PMID:25877329</ref> <ref name="Abramowicz">PMID:25182393</ref>
 == Function ==