Neurofibromin: Difference between revisions
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[[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===== | ||
The <scene name='90/904326/Open/1'>open state</scene> of neurofibromin has one protomer in a open conformation and the other in a closed conformation. The protomer in the open conformation allows for the binding of Ras because of reorientation of the GRD and Sec14-PH domains. In the open conformation, the metal binding site found in the closed conformation is lost due to separation of the N-HEAT/ARM and the cysteine residue from the histidine residues founds in the GRD-Sec14-PH linker. The loss of the metal binding site allows for Ras to bind to the Gap-related domain due to the loss of steric hinderance. | The <scene name='90/904326/Open/1'>open state</scene> of neurofibromin has one protomer in a open conformation and the other in a closed conformation. The protomer in the open conformation allows for the binding of Ras because of reorientation of the GRD and Sec14-PH domains. In the open conformation, the metal binding site found in the closed conformation is lost due to separation of the N-HEAT/ARM and the cysteine residue from the histidine residues founds in the GRD-Sec14-PH linker. The loss of the metal binding site in one of the monomers allows for Ras to bind to the Gap-related domain due to the loss of steric hinderance. | ||
=====Transition Between Open and Closed Conformation===== | =====Transition Between Open and Closed Conformation===== | ||
In the transition from the closed state to the open state, several of the domains of neurofibromin rotate to make the binding site of neurofibromin more accessible . This rotation is able to occur due to the rotation of three connective linkers, L1, L2, and L3. <scene name='90/904326/L1/1'>L1</scene> is located between an alpha helix 48 in N-HEAT and an alpha helix 49 in GRD. G1190 is a potential hinge point when L1 rotates and pushes the alpha helices outwards to move the Gap-related domain. <scene name='90/904326/L3/1'>L3</scene> is located between the Sec14-PH domain and the C-HEAT/ARM and aids in the movement of the Sec14-PH domain. The proximity of L1 and L3 has to be close to facilitate the rotation of the domains. <scene name='90/904326/L2/1'>L2</scene> starts at the last helix in the Gap-related domain and extends to the Sec14-PH domain. Its primary role is to move the Sec14-PH domain away from the GRD. Without these rotations, the membrane binding sites are occluded and inaccessible. <ref name="Naschberger"/> | In the transition from the closed state to the open state, several of the domains of neurofibromin rotate to make the binding site of neurofibromin more accessible . This rotation is able to occur due to the rotation of three connective linkers, L1, L2, and L3. <scene name='90/904326/L1/1'>L1</scene> is located between an alpha helix 48 in N-HEAT and an alpha helix 49 in GRD. G1190 is a potential hinge point when L1 rotates and pushes the alpha helices outwards to move the Gap-related domain. <scene name='90/904326/L3/1'>L3</scene> is located between the Sec14-PH domain and the C-HEAT/ARM and aids in the movement of the Sec14-PH domain. The proximity of L1 and L3 has to be close to facilitate the rotation of the domains. <scene name='90/904326/L2/1'>L2</scene> starts at the last helix in the Gap-related domain and extends to the Sec14-PH domain. Its primary role is to move the Sec14-PH domain away from the GRD. Without these rotations, the membrane binding sites are occluded and inaccessible. <ref name="Naschberger"/> | ||
