Sandbox Reserved 1710: Difference between revisions

In the <scene name='90/904315/Open_conformation/4'>open, active conformation</scene>, the GRD and Sec14-PH domain on one protomer have [https://youtu.be/I1I4uTVFR00 rotated] and become accessible for binding to Ras. This transition is initiated by the movement of the transition metal-binding site. The Cys 1032, His 1558, and His 1576 Residues become separated and zinc is not able to bond. In the active form, one protomer has its GRD and Sec14-PH domains oriented oppositely from the inactive form (Figure 4). The GRD rotates -130° and the Sec14-PH domain rotates -90° away from the N-HEAT/ARM. Due to this rotation, Cys 1032 is now located too far away, approximately 30 Å, from His 1558 and His 1576 which results in the loss of the metal-binding site and no formation of the <scene name='90/904315/Open_conformation_triade/6'>triad</scene>. The lack of the transition metal-binding site allows the GRD to orient itself to <scene name='90/904315/Openwithras/1'>associate with Ras</scene><ref name="Naschberger">PMID:34707296</ref>. This association positions the Arginine Finger to help stabilize and orient a catalytic Ras residue (Q61) so that the gamma phosphate of GTP can be nucleophilically attacked <ref>PMID:33121128</ref>. When Neurofibromin is in the open, active conformation, Arg 1276 is able to bind to Ras because there is no steric hindrance from the Neurofibromin core.<ref name="Naschberger">PMID:34707296</ref>