Sandbox Reserved 1706: Difference between revisions

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==Introduction==

[https://en.wikipedia.org/wiki/Neurofibromatosis_type_I Neurofibromatosis Type 1] is a genetic disorder caused by mutations in the tumor suppressor gene NF1 that codes for the [https://en.wikipedia.org/wiki/GTPase-activating_protein GTPase-activating protein] neurofibromin. Neurofibromin is closely involved in signaling pathways such as [https://en.wikipedia.org/wiki/MAPK/ERK_pathway ~~MARP~~/ERK], [https://en.wikipedia.org/wiki/PI3K/AKT/mTOR_pathway P13K/AKT/mTOR], and other cell signaling pathways that use [https://en.wikipedia.org/wiki/Ras_GTPase Ras] <ref name="Bergoug"> DOI:10.3390/cells9112365</ref>. Mutations that cause a decrease in activity of neurofibromin cause tumors to grow along your nerves. As neurofibromin is ubiquitously expressed throughout the body, these tumors can grow anywhere. Neurofibromin is located in the [https://en.wikipedia.org/wiki/Cytosol cytosol] of the cell but is recruited to the [https://en.wikipedia.org/wiki/Cell_membrane plasma membrane] to bind to [https://en.wikipedia.org/wiki/Ras_GTPase Ras]. The structure of neurofibromin was detemed through high-resolution single particles [https://en.wikipedia.org/wiki/Cryogenic_electron_microscopy cryogenic electron microscopy] to understand the overall structure and the different domains. [https://en.wikipedia.org/wiki/X-ray_crystallography#:~:text=X%2Dray%20crystallography%20is%20the,diffract%20into%20many%20specific%20directions. X-Ray crystallography] experiments found inconsistency in the structural determination.<ref name="Bergoug"> DOI:10.3390/cells9112365</ref><ref name="Bourne"> DOI:10.1038/39470</ref><ref name="Lupton"> DOI:10.1038/s41594-021-00687-2</ref><ref name="Naschberger"> DOI:10.1038/s41586-021-04024-x</ref>

[https://en.wikipedia.org/wiki/Neurofibromatosis_type_I Neurofibromatosis Type 1] is a genetic disorder caused by mutations in the tumor suppressor gene NF1 that codes for the [https://en.wikipedia.org/wiki/GTPase-activating_protein GTPase-activating protein] neurofibromin. Neurofibromin is closely involved in signaling pathways such as [https://en.wikipedia.org/wiki/MAPK/ERK_pathway MAPK/ERK], [https://en.wikipedia.org/wiki/PI3K/AKT/mTOR_pathway P13K/AKT/mTOR], and other cell signaling pathways that use [https://en.wikipedia.org/wiki/Ras_GTPase Ras] <ref name="Bergoug"> DOI:10.3390/cells9112365</ref>. Mutations that cause a decrease in activity of neurofibromin cause tumors to grow along your nerves. As neurofibromin is ubiquitously expressed throughout the body, these tumors can grow anywhere. Neurofibromin is located in the [https://en.wikipedia.org/wiki/Cytosol cytosol] of the cell but is recruited to the [https://en.wikipedia.org/wiki/Cell_membrane plasma membrane] to bind to [https://en.wikipedia.org/wiki/Ras_GTPase Ras]. The structure of neurofibromin was detemed through high-resolution single particles [https://en.wikipedia.org/wiki/Cryogenic_electron_microscopy cryogenic electron microscopy] to understand the overall structure and the different domains. [https://en.wikipedia.org/wiki/X-ray_crystallography#:~:text=X%2Dray%20crystallography%20is%20the,diffract%20into%20many%20specific%20directions. X-Ray crystallography] experiments found inconsistency in the structural determination.<ref name="Bergoug"> DOI:10.3390/cells9112365</ref><ref name="Bourne"> DOI:10.1038/39470</ref><ref name="Lupton"> DOI:10.1038/s41594-021-00687-2</ref><ref name="Naschberger"> DOI:10.1038/s41586-021-04024-x</ref>

==Function==

Neurofibromin is a [https://en.wikipedia.org/wiki/GTPase-activating_protein GTPase-activating protein] that binds to [https://en.wikipedia.org/wiki/Ras_GTPase Ras], a [https://en.wikipedia.org/wiki/GTPase GTPase], to increase the hydrolysis of GTP to GDP. This inactivates the cell signaling of Ras until another [https://en.wikipedia.org/wiki/Guanosine_triphosphate GTP] can replace the [https://en.wikipedia.org/wiki/Guanosine_diphosphate GDP] from the cytosol. Neurofibromin and Ras binding is possible in only the <scene name='90/904311/Open_conformation/2'>open conformation</scene> of Neurofibromin. The mechanism is shown in figure 1 and displays the slow hydrolysis of GTP bound to Ras and the fast hydrolysis of GTP when bound to Neurofibromin. <ref name="Bourne"> DOI:10.1038/39470</ref><ref name="Lupton"> DOI:10.1038/s41594-021-00687-2</ref><ref name="Naschberger"> DOI:10.1038/s41586-021-04024-x</ref> [[Image:RasNeurofibrominMech.PNG|300px|right|thumb|Figure 1: Diagram of Ras GTP hydrolysis when bound to neurofibromin and unbound. The speed of GTP hydrolysis is significantly increased when bound to neurofibromin. Ras is inactive when bound to GDP and active when bound to GTP ]]

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 ==Introduction==
-[https://en.wikipedia.org/wiki/Neurofibromatosis_type_I Neurofibromatosis Type 1] is a genetic disorder caused by mutations in the tumor suppressor gene NF1 that codes for the [https://en.wikipedia.org/wiki/GTPase-activating_protein GTPase-activating protein] neurofibromin. Neurofibromin is closely involved in signaling pathways such as [https://en.wikipedia.org/wiki/MAPK/ERK_pathway MARP/ERK], [https://en.wikipedia.org/wiki/PI3K/AKT/mTOR_pathway P13K/AKT/mTOR], and other cell signaling pathways that use [https://en.wikipedia.org/wiki/Ras_GTPase Ras] <ref name="Bergoug"> DOI:10.3390/cells9112365</ref>. Mutations that cause a decrease in activity of neurofibromin cause tumors to grow along your nerves. As neurofibromin is ubiquitously expressed throughout the body, these tumors can grow anywhere. Neurofibromin is located in the [https://en.wikipedia.org/wiki/Cytosol cytosol] of the cell but is recruited to the [https://en.wikipedia.org/wiki/Cell_membrane plasma membrane] to bind to [https://en.wikipedia.org/wiki/Ras_GTPase Ras]. The structure of neurofibromin was detemed through high-resolution single particles [https://en.wikipedia.org/wiki/Cryogenic_electron_microscopy cryogenic electron microscopy] to understand the overall structure and the different domains. [https://en.wikipedia.org/wiki/X-ray_crystallography#:~:text=X%2Dray%20crystallography%20is%20the,diffract%20into%20many%20specific%20directions. X-Ray crystallography] experiments found inconsistency in the structural determination.<ref name="Bergoug"> DOI:10.3390/cells9112365</ref><ref name="Bourne"> DOI:10.1038/39470</ref><ref name="Lupton"> DOI:10.1038/s41594-021-00687-2</ref><ref name="Naschberger"> DOI:10.1038/s41586-021-04024-x</ref>
+[https://en.wikipedia.org/wiki/Neurofibromatosis_type_I Neurofibromatosis Type 1] is a genetic disorder caused by mutations in the tumor suppressor gene NF1 that codes for the [https://en.wikipedia.org/wiki/GTPase-activating_protein GTPase-activating protein] neurofibromin. Neurofibromin is closely involved in signaling pathways such as [https://en.wikipedia.org/wiki/MAPK/ERK_pathway MAPK/ERK], [https://en.wikipedia.org/wiki/PI3K/AKT/mTOR_pathway P13K/AKT/mTOR], and other cell signaling pathways that use [https://en.wikipedia.org/wiki/Ras_GTPase Ras] <ref name="Bergoug"> DOI:10.3390/cells9112365</ref>. Mutations that cause a decrease in activity of neurofibromin cause tumors to grow along your nerves. As neurofibromin is ubiquitously expressed throughout the body, these tumors can grow anywhere. Neurofibromin is located in the [https://en.wikipedia.org/wiki/Cytosol cytosol] of the cell but is recruited to the [https://en.wikipedia.org/wiki/Cell_membrane plasma membrane] to bind to [https://en.wikipedia.org/wiki/Ras_GTPase Ras]. The structure of neurofibromin was detemed through high-resolution single particles [https://en.wikipedia.org/wiki/Cryogenic_electron_microscopy cryogenic electron microscopy] to understand the overall structure and the different domains. [https://en.wikipedia.org/wiki/X-ray_crystallography#:~:text=X%2Dray%20crystallography%20is%20the,diffract%20into%20many%20specific%20directions. X-Ray crystallography] experiments found inconsistency in the structural determination.<ref name="Bergoug"> DOI:10.3390/cells9112365</ref><ref name="Bourne"> DOI:10.1038/39470</ref><ref name="Lupton"> DOI:10.1038/s41594-021-00687-2</ref><ref name="Naschberger"> DOI:10.1038/s41586-021-04024-x</ref>
 ==Function==
 Neurofibromin is a [https://en.wikipedia.org/wiki/GTPase-activating_protein GTPase-activating protein] that binds to [https://en.wikipedia.org/wiki/Ras_GTPase Ras], a [https://en.wikipedia.org/wiki/GTPase GTPase], to increase the hydrolysis of GTP to GDP. This inactivates the cell signaling of Ras until another [https://en.wikipedia.org/wiki/Guanosine_triphosphate GTP] can replace the [https://en.wikipedia.org/wiki/Guanosine_diphosphate GDP] from the cytosol. Neurofibromin and Ras binding is possible in only the <scene name='90/904311/Open_conformation/2'>open conformation</scene> of Neurofibromin. The mechanism is shown in figure 1 and displays the slow hydrolysis of GTP bound to Ras and the fast hydrolysis of GTP when bound to Neurofibromin. <ref name="Bourne"> DOI:10.1038/39470</ref><ref name="Lupton"> DOI:10.1038/s41594-021-00687-2</ref><ref name="Naschberger"> DOI:10.1038/s41586-021-04024-x</ref> [[Image:RasNeurofibrominMech.PNG|300px|right|thumb|Figure 1: Diagram of Ras GTP hydrolysis when bound to neurofibromin and unbound. The speed of GTP hydrolysis is significantly increased when bound to neurofibromin. Ras is inactive when bound to GDP and active when bound to GTP  ]]