Neurofibromin: Difference between revisions
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Neurofibromin is a large protein of 2818 amino acids <ref>DOI 10.3390/cells9112365</ref> and is a homodimer that exists in two conformations. | Neurofibromin is a large protein of 2818 amino acids <ref>DOI 10.3390/cells9112365</ref> and is a homodimer that exists in two conformations. | ||
===Domains=== | ===Domains=== | ||
Neurofibromin consists of multiple domains. A few notable ones are the N-HEAT/ARM, GRD, Sec14-PH, and C-HEAT/ARM. The two most characterized domains of neurofibromin are the Sec14-PH and GRD domains. Each of the protomers of neurofibromin contains these domains. | Neurofibromin consists of multiple domains. (Figure 1). A few notable ones are the N-HEAT/ARM, GRD, Sec14-PH, and C-HEAT/ARM. The two most characterized domains of neurofibromin are the Sec14-PH and GRD domains. Each of the protomers of neurofibromin contains these domains. | ||
[[Image:domainsneurofibromin.png|500 px|thumb|Figure 1. Domains of Neurofibromin.]] | [[Image:domainsneurofibromin.png|500 px|thumb|Figure 1. Domains of Neurofibromin.]] | ||
====N-HEAT/ARM and C-HEAT/ARM==== | ====N-HEAT/ARM and C-HEAT/ARM==== | ||
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===Important Structural Features=== | ===Important Structural Features=== | ||
====Conformations==== | ====Conformations==== | ||
The two conformations that neurofibromin exists in are the open state and closed state. The conformational change of neurofibromin involves rearrangement of the domains. | |||
=====Closed Conformation===== | =====Closed Conformation===== | ||
The <scene name='90/904326/Closed_conformation/3'>closed state</scene> of neurofibromin has both protomers in a closed conformation, which inhibits the binding of Ras to the GRD of neurofibromin due to the HEAT/ARM blocking the GRD. A metal binding site between the N-HEAT/ARM domain and the GRD-Sec14-PH linker stabilize the closed conformation. This site is coordinated by three residues, C1032, H1558, and H1576, and a water molecule. This binding site is preferential for zinc; zinc has been found to stabilize the closed conformation of neurofibromin. In the absence of zinc, | The <scene name='90/904326/Closed_conformation/3'>closed state</scene> of neurofibromin has both protomers in a closed conformation, which inhibits the binding of Ras to the GRD of neurofibromin due to the HEAT/ARM blocking the GRD. A metal binding site between the N-HEAT/ARM domain and the GRD-Sec14-PH linker stabilize the closed conformation. This site is coordinated by three residues, C1032, H1558, and H1576, and a water molecule. This binding site is preferential for zinc; zinc has been found to stabilize the closed conformation of neurofibromin. In the absence of zinc, neurofibromin is in the open conformation. | ||
[[Image:greenTriad.png|200 px|thumb|Figure 2. Triad of Residues that keep Neurofibromin in the Closed Conformation.]] | [[Image:greenTriad.png|200 px|thumb|Figure 2. Triad of Residues that keep Neurofibromin in the Closed Conformation.]] | ||
=====Open Conformation===== | =====Open Conformation===== | ||
