Neurofibromin: Difference between revisions

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[https://en.wikipedia.org/wiki/HEAT_repeat Heat domains] are domains found in cytoplasmic proteins that consist of four different proteins: Huntingtin, elongation factor 3, protein phosphatase 2A, and TOR1. <ref name= ''Yoshimura''>DOI: 10.1242/jcs.185710</ref>. The HEAT/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 closed conformation, the HEAT/ARM domains cover the GRD, preventing the binding of Ras through steric hinderance. <ref>DOI 10.1038/s41594-021-00687-2</ref>

==== GRD domain ====

The Gap-related domain, or GRD, is the catalytic domain of neurofibromin. This domain also contains a tubulin-binding domain. 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/Open_conformation_with_grd_hig/3'>open </scene> and <scene name='90/904326/Grd_closed_conformation/3'>closed</scene> conformations of neurofibromin.

The Gap-related domain, or GRD, is the catalytic domain of neurofibromin. It ranges from residues 1196 to 1547. <ref>DOI 10.1038/s41586-021-04024-x</ref> This domain also contains a tubulin-binding domain. 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/Open_conformation_with_grd_hig/3'>open </scene> and <scene name='90/904326/Grd_closed_conformation/3'>closed</scene> conformations of neurofibromin.

==== SEC-PH ====

The Sec-PH domain is the lipid-binding domain of neurofibromin. In the <scene name='90/904326/Sec14ph_and_grd_closed/4'>closed conformation</scene> of neurofibromin, the hydrophobic core is blocked by the Gap-related domain. The <scene name='90/904326/Sec15ph_and_grd_open/4'>open conformation</scene> allows the hydrophobic core in the Sec cavity to be accessible and exposed.

The Sec-PH domain is the lipid-binding domain of neurofibromin, found in residues 1565 to 1835. <ref>DOI 10.1038/s41586-021-04024-x</ref> In the <scene name='90/904326/Sec14ph_and_grd_closed/4'>closed conformation</scene> of neurofibromin, the hydrophobic core is blocked by the Gap-related domain. The <scene name='90/904326/Sec15ph_and_grd_open/4'>open conformation</scene> allows the hydrophobic core in the Sec cavity to be accessible and exposed.

==== CSRD and CTD ====

The Cysteine-Serine-rich domain (CSRD) and C-terminal domain (CTD) contain phosphorylation sites. The CSRD is able to be phosphorylated by protein kinases [https://en.wikipedia.org/wiki/Protein_kinase_A A] and [https://en.wikipedia.org/wiki/Protein_kinase_C C] Phosphorylation by protein kinase C is a positive regulator of neurofibromin activity. The CTD is phosphorylated primarily by protein kinase C. This domain is a negative regulator of neurofibromin activity if particular residues are phosphorylated. CTD contains a nuclear localization signal as well.

Neurofibromin: Difference between revisions

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@@ Line 10: / Line 10: @@
 [https://en.wikipedia.org/wiki/HEAT_repeat Heat domains] are domains found in cytoplasmic proteins that consist of four different proteins: Huntingtin, elongation factor 3, protein phosphatase 2A, and TOR1. <ref name= ''Yoshimura''>DOI: 10.1242/jcs.185710</ref>. The HEAT/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 closed conformation, the HEAT/ARM domains cover the GRD, preventing the binding of Ras through steric hinderance. <ref>DOI 10.1038/s41594-021-00687-2</ref>
 ==== GRD domain ====
-The Gap-related domain, or GRD, is the catalytic domain of neurofibromin. This domain also contains a tubulin-binding domain. 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/Open_conformation_with_grd_hig/3'>open </scene> and <scene name='90/904326/Grd_closed_conformation/3'>closed</scene> conformations of neurofibromin.
+The Gap-related domain, or GRD, is the catalytic domain of neurofibromin. It ranges from residues 1196 to 1547. <ref>DOI 10.1038/s41586-021-04024-x</ref> This domain also contains a tubulin-binding domain. 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/Open_conformation_with_grd_hig/3'>open </scene> and <scene name='90/904326/Grd_closed_conformation/3'>closed</scene> conformations of neurofibromin.
 ==== SEC-PH ====
-The Sec-PH domain is the lipid-binding domain of neurofibromin. In the <scene name='90/904326/Sec14ph_and_grd_closed/4'>closed conformation</scene> of neurofibromin, the hydrophobic core is blocked by the Gap-related domain. The <scene name='90/904326/Sec15ph_and_grd_open/4'>open conformation</scene> allows the hydrophobic core in the Sec cavity to be accessible and exposed.
+The Sec-PH domain is the lipid-binding domain of neurofibromin, found in residues 1565 to 1835. <ref>DOI 10.1038/s41586-021-04024-x</ref> In the <scene name='90/904326/Sec14ph_and_grd_closed/4'>closed conformation</scene> of neurofibromin, the hydrophobic core is blocked by the Gap-related domain. The <scene name='90/904326/Sec15ph_and_grd_open/4'>open conformation</scene> allows the hydrophobic core in the Sec cavity to be accessible and exposed.
 ==== CSRD and CTD ====
 The Cysteine-Serine-rich domain (CSRD) and C-terminal domain (CTD) contain phosphorylation sites. The CSRD is able to be phosphorylated by protein kinases [https://en.wikipedia.org/wiki/Protein_kinase_A A] and [https://en.wikipedia.org/wiki/Protein_kinase_C C] Phosphorylation by protein kinase C is a positive regulator of neurofibromin activity. The CTD is phosphorylated primarily by protein kinase C. This domain is a negative regulator of neurofibromin activity if particular residues are phosphorylated. CTD contains a nuclear localization signal as well.