Neurofibromin: Difference between revisions
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<StructureSection load='' scene='90/904325/Introductory_image_full/2' size='340' side='right' caption='Neurofibromin [https://www.rcsb.org/structure/7PGS (7pgs)] Homo dimeric structure colored to differentiate dimers'> | <scene name='90/904326/Heat/1'>Text To Be Displayed</scene><StructureSection load='' scene='90/904325/Introductory_image_full/2' size='340' side='right' caption='Neurofibromin [https://www.rcsb.org/structure/7PGS (7pgs)] Homo dimeric structure colored to differentiate dimers'> | ||
== Introduction == | == Introduction == | ||
<scene name='90/904325/Introductory_image_full/1'>Neurofibromin</scene> (NF) is a cytoplasmic protein encoded by the ''NF1'' gene located on chromosome 17 <ref name= "Bergoug">PMID:33121128</ref>. It is localized to the cell membrane by the [https://en.wikipedia.org/wiki/SPRED1 SPRED 1] protein<ref name= "Naschberger">PMID:34707296</ref>. The neurofibromin protein in encoded by over 350 kb of DNA and contains 62 exons, 58 of which are constitutive<ref name= ''Trovó-Marqui''>PMID:16813595</ref>. NF suppresses the <scene name='90/904325/Ras_neurofibromin_overview/1'>Ras</scene> oncogene by increasing the rate of hydrolysis from <scene name='90/904325/Arginine_finger_and_gtp/3'>Ras bound to GTP</scene> (active) to <scene name='90/904325/Arginine_finger_and_gdp/4'>Ras bound to GDP</scene> (inactive)<ref name= ''Hall''>PMID:12213964</ref>. Increasing the rate of Ras inactivation decreases cell proliferation linked to cancer<ref name= ''Cimino''>PMID:29478615</ref>. | <scene name='90/904325/Introductory_image_full/1'>Neurofibromin</scene> (NF) is a cytoplasmic protein encoded by the ''NF1'' gene located on chromosome 17 <ref name= "Bergoug">PMID:33121128</ref>. It is localized to the cell membrane by the [https://en.wikipedia.org/wiki/SPRED1 SPRED 1] protein<ref name= "Naschberger">PMID:34707296</ref>. The neurofibromin protein in encoded by over 350 kb of DNA and contains 62 exons, 58 of which are constitutive<ref name= ''Trovó-Marqui''>PMID:16813595</ref>. NF suppresses the <scene name='90/904325/Ras_neurofibromin_overview/1'>Ras</scene> oncogene by increasing the rate of hydrolysis from <scene name='90/904325/Arginine_finger_and_gtp/3'>Ras bound to GTP</scene> (active) to <scene name='90/904325/Arginine_finger_and_gdp/4'>Ras bound to GDP</scene> (inactive)<ref name= ''Hall''>PMID:12213964</ref>. Increasing the rate of Ras inactivation decreases cell proliferation linked to cancer<ref name= ''Cimino''>PMID:29478615</ref>. | ||
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[[Image:domainsneurofibromin.png|500 px|thumb|Figure 1. Representation of the Domains of Neurofibromin. Shown are the most characterized domains, Gap-related and Sec14-PH, connected to the N and C-HEAT/ARMs. Each of the domains of Neurofibromin can be found in both of the monomers.]] | [[Image:domainsneurofibromin.png|500 px|thumb|Figure 1. Representation of the Domains of Neurofibromin. Shown are the most characterized domains, Gap-related and Sec14-PH, connected to the N and C-HEAT/ARMs. Each of the domains of Neurofibromin can be found in both of the monomers.]] | ||
====N-HEAT/ARM and C-HEAT/ARM==== | ====N-HEAT/ARM and C-HEAT/ARM==== | ||
[https://en.wikipedia.org/wiki/HEAT_repeat Heat domains] are domains found in cytoplasmic proteins that consist of four different proteins: [https://proteopedia.org/wiki/index.php/Huntingtin Huntingtin], [https://proteopedia.org/wiki/index.php/Elongation_factor elongation factor 3], [https://proteopedia.org/wiki/index.php/Protein_phosphatase protein phosphatase 2A], and TOR1. <ref name= ''Yoshimura''>DOI: 10.1242/jcs.185710</ref>. The [https://en.wikipedia.org/wiki/HEAT_repeat HEAT] / [https://en.wikipedia.org/wiki/Armadillo_repeat ARM] cores are made up of many alpha helices. The N-HEAT/ARM and C-HEAT/ARM are rigid, which makes them critical in the rearrangement of the Gap-related and Sec14-PH domains. In the <scene name='90/ | [https://en.wikipedia.org/wiki/HEAT_repeat Heat domains] are domains found in cytoplasmic proteins that consist of four different proteins: [https://proteopedia.org/wiki/index.php/Huntingtin Huntingtin], [https://proteopedia.org/wiki/index.php/Elongation_factor elongation factor 3], [https://proteopedia.org/wiki/index.php/Protein_phosphatase protein phosphatase 2A], and TOR1. <ref name= ''Yoshimura''>DOI: 10.1242/jcs.185710</ref>. The [https://en.wikipedia.org/wiki/HEAT_repeat HEAT] / [https://en.wikipedia.org/wiki/Armadillo_repeat ARM] cores are made up of many alpha helices. The N-HEAT/ARM and C-HEAT/ARM are rigid, which makes them critical in the rearrangement of the Gap-related and Sec14-PH domains. In the <scene name='90/904325/Heat/1'>closed conformation</scene>, the HEAT/ARM domains cover the GRD, preventing the binding of Ras through steric hinderance. <ref name= "Lupton">DOI 10.1038/s41594-021-00687-2</ref> | ||
==== GRD domain ==== | ==== GRD domain ==== | ||
The Gap-related domain, or <scene name='90/904326/Grd_highlighted/1'>GRD</scene>, is the catalytic domain of neurofibromin. It ranges from residues 1196 to 1547. <ref name="Naschberger"/> Its main catalytic mechanism is the hydrolysis of GTP-bound Ras into GDP-bound Ras, which converts Ras from its active form into its inactive form. The GRD provides an arginine residue, known as the arginine finger, to Ras. The location of the Gap-related domain is shifted between the <scene name='90/904326/Grdopen/1'>open conformation</scene> and closed conformations of neurofibromin. | The Gap-related domain, or <scene name='90/904326/Grd_highlighted/1'>GRD</scene>, is the catalytic domain of neurofibromin. It ranges from residues 1196 to 1547. <ref name="Naschberger"/> Its main catalytic mechanism is the hydrolysis of GTP-bound Ras into GDP-bound Ras, which converts Ras from its active form into its inactive form. The GRD provides an arginine residue, known as the arginine finger, to Ras. The location of the Gap-related domain is shifted between the <scene name='90/904326/Grdopen/1'>open conformation</scene> and closed conformations of neurofibromin. | ||
