Neurofibromin: Difference between revisions
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== Structure == | == Structure == | ||
===Domains=== | ===Domains=== | ||
[[Image:Nfdomains2.png|800 px|thumb|Figure 1. Domains of Neurofibromin.]] | [[Image:Nfdomains2.png|800 px|thumb|Figure 1. Domains of Neurofibromin.]] | ||
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The Cysteine-Serine-rich domain (CSRD) and C-terminal domain (CTD) contain phosphorylation sites. The CSRD is able to be phosphorylated by protein kinases A and 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. It also plays an important role in tubulin binding, as it helps in the transition from metaphase to anaphase. CTD contains a nuclear localization signal as well. | The Cysteine-Serine-rich domain (CSRD) and C-terminal domain (CTD) contain phosphorylation sites. The CSRD is able to be phosphorylated by protein kinases A and 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. It also plays an important role in tubulin binding, as it helps in the transition from metaphase to anaphase. CTD contains a nuclear localization signal as well. | ||
===Important Structural Features=== | ===Important Structural Features=== | ||
==== | ====Conformations==== | ||
Neurofibromin is a dimeric protein that is found in the cytoplasm. It exists in two conformations, <scene name='90/904326/Open_conformation/2'>open</scene> and <scene name='90/904326/Closed_conformation/2'>closed</scene> . The open conformation has one of the protomers in an auto-inhibited conformation and the other in an open conformation. In the <scene name='90/904326/Open_conformation_with_grd_hig/2'>open conformation</scene>, Ras is able to bind to the GRD neurofibromin. The <scene name='90/904326/Grd_closed_conformation/2'>closed conformation</scene> has both protomers in an autoinhibited conformation, which sterically hinders the binding of Ras to GRD. Only one of the protomers has to be in the open conformation for Ras to bind. | |||
====Ras binding site==== | |||
Ras and Neurofibromin associate through an arginine residue, 1276, that comes from neurofibromin. This arginine is referred to as the [http://https://en.wikipedia.org/wiki/Arginine_finger “arginine finger”] and assists in the hydrolysis of GTP by binding to a backbone carbon atom of tyrosine 32 of Ras when neurofibromin is in the open conformation. It points into the GTP binding site of Ras when neurofibromin is in the open conformation. R1276 also helps stabilize the position of Glutamine 61, a key catalytic residue, through hydrogen bonds. | Ras and Neurofibromin associate through an arginine residue, 1276, that comes from neurofibromin. This arginine is referred to as the [http://https://en.wikipedia.org/wiki/Arginine_finger “arginine finger”] and assists in the hydrolysis of GTP by binding to a backbone carbon atom of tyrosine 32 of Ras when neurofibromin is in the open conformation. It points into the GTP binding site of Ras when neurofibromin is in the open conformation. R1276 also helps stabilize the position of Glutamine 61, a key catalytic residue, through hydrogen bonds. | ||
