Sandbox Reserved 1710: Difference between revisions

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=== Open Conformation ===

The other conformation that characterizes Neurofibromin is the <scene name='90/904315/Open_conformation/3'>Open Conformation</scene>. In the open conformation of Neurofibromin, the protein is considered active and is participating in its function of Ras regulation. This occurs because the transition metal-binding site with zinc no longer is able to form due to an increase in distance between the C1032, H1558 and H1576 residues that form the <scene name='90/904315/Open_conformation_triade/4'>Open Triade</scene>. One protomer in Neurofibromin has its GRD and Sec14-PH domains oriented in way that is almost reversed in position compared to the closed conformation. Due to this rotation, C1032 is now located too far away, approximately 30 Angstroms, from H1558 and H1576 which results in the loss of the metal-binding site. The lack of the transition metal-binding site allows the GRD to orient itself in such a way that it can associate with <scene name='90/904315/Ras_open_conformation/2'>Ras in the Open Conformation</scene>. The reason that Neurofibromin is only able to associate with Ras in the open conformation is due to one critical residue, the <scene name='90/904315/Open_conformation_arginine_fin/2'>Arginine Finger</scene> located at position 1276 in Neurofibromin. When Neurofibromin is in the open conformation, R1276 is able to <scene name='90/904315/Ras_open_conformation_with_arg/2'>bind to Ras</scene> because there is no steric hindrance from the Neurofibromin core.

The other conformation that characterizes Neurofibromin is the <scene name='90/904315/Open_conformation/3'>Open Conformation</scene>. In the open conformation of Neurofibromin, the protein is considered active and is participating in its function of Ras regulation. This occurs because the transition metal-binding site with zinc no longer is able to form due to an increase in distance between the C1032, H1558 and H1576 residues that form the <scene name='90/904315/Open_conformation_triade/4'>Open Triade</scene>. One protomer in Neurofibromin has its GRD and Sec14-PH domains oriented in way that is almost reversed in position compared to the closed conformation. The GRD rotates -130° and the Sec14-PH domain rotates -90° in the transition between the closed and the open conformation. Due to this rotation, C1032 is now located too far away, approximately 30 Angstroms, from H1558 and H1576 which results in the loss of the metal-binding site. The lack of the transition metal-binding site allows the GRD to orient itself in such a way that it can associate with <scene name='90/904315/Ras_open_conformation/2'>Ras in the Open Conformation</scene>. The reason that Neurofibromin is only able to associate with Ras in the open conformation is due to one critical residue, the <scene name='90/904315/Open_conformation_arginine_fin/2'>Arginine Finger</scene> located at position 1276 in Neurofibromin. When Neurofibromin is in the open conformation, R1276 is able to <scene name='90/904315/Ras_open_conformation_with_arg/2'>bind to Ras</scene> because there is no steric hindrance from the Neurofibromin core.

[[Image:GRDandSec14PHRotation.jpg|340 px|left|thumb|Rotation of the GRD and Sec14-PH domains from the closed conformation of neurofibromin to the open conformation of neurofibromin to allow Ras binding. The GRD rotates -130° and the Sec14-PH domain rotates -90°]]

Sandbox Reserved 1710: Difference between revisions

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 === Open Conformation ===
-The other conformation that characterizes Neurofibromin is the <scene name='90/904315/Open_conformation/3'>Open Conformation</scene>. In the open conformation of Neurofibromin, the protein is considered active and is participating in its function of Ras regulation. This occurs because the transition metal-binding site with zinc no longer is able to form due to an increase in distance between the C1032, H1558 and H1576 residues that form the <scene name='90/904315/Open_conformation_triade/4'>Open Triade</scene>. One protomer in Neurofibromin has its GRD and Sec14-PH domains oriented in way that is almost reversed in position compared to the closed conformation. Due to this rotation, C1032 is now located too far away, approximately 30 Angstroms, from H1558 and H1576 which results in the loss of the metal-binding site. The lack of the transition metal-binding site allows the GRD to orient itself in such a way that it can associate with <scene name='90/904315/Ras_open_conformation/2'>Ras in the Open Conformation</scene>. The reason that Neurofibromin is only able to associate with Ras in the open conformation is due to one critical residue, the <scene name='90/904315/Open_conformation_arginine_fin/2'>Arginine Finger</scene> located at position 1276 in Neurofibromin. When Neurofibromin is in the open conformation, R1276 is able to <scene name='90/904315/Ras_open_conformation_with_arg/2'>bind to Ras</scene> because there is no steric hindrance from the Neurofibromin core.
+The other conformation that characterizes Neurofibromin is the <scene name='90/904315/Open_conformation/3'>Open Conformation</scene>. In the open conformation of Neurofibromin, the protein is considered active and is participating in its function of Ras regulation. This occurs because the transition metal-binding site with zinc no longer is able to form due to an increase in distance between the C1032, H1558 and H1576 residues that form the <scene name='90/904315/Open_conformation_triade/4'>Open Triade</scene>. One protomer in Neurofibromin has its GRD and Sec14-PH domains oriented in way that is almost reversed in position compared to the closed conformation. The GRD rotates -130° and the Sec14-PH domain rotates -90° in the transition between the closed and the open conformation. Due to this rotation, C1032 is now located too far away, approximately 30 Angstroms, from H1558 and H1576 which results in the loss of the metal-binding site. The lack of the transition metal-binding site allows the GRD to orient itself in such a way that it can associate with <scene name='90/904315/Ras_open_conformation/2'>Ras in the Open Conformation</scene>. The reason that Neurofibromin is only able to associate with Ras in the open conformation is due to one critical residue, the <scene name='90/904315/Open_conformation_arginine_fin/2'>Arginine Finger</scene> located at position 1276 in Neurofibromin. When Neurofibromin is in the open conformation, R1276 is able to <scene name='90/904315/Ras_open_conformation_with_arg/2'>bind to Ras</scene> because there is no steric hindrance from the Neurofibromin core.
 [[Image:GRDandSec14PHRotation.jpg|340 px|left|thumb|Rotation of the GRD and Sec14-PH domains from the closed conformation of neurofibromin to the open conformation of neurofibromin to allow Ras binding. The GRD rotates -130° and the Sec14-PH domain rotates -90°]]