Sandbox Reserved 1706

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side='right' caption='NF1 Closed Confirmation 7PGR' scene=’’>
side='right' caption='NF1 Closed Confirmation 7PGR' scene=’’>
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<scene name='90/904311/Closed_confirmation/1'>Closed confirmation Spinning</scene>
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==Introduction==
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==History==
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<scene name='90/904311/Open_confirmation/1'>Open confirmation</scene>
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==Function==
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NF1 is a GTPase-activation protein that binds to RAS to increase the hydrolysis of GTP to GDP. This inactivates the cell signaling of Ras until another GTP can replace the GDP from the cytosol. NF1 and Ras binding is possible in only the <scene name='90/904311/Open_conformation/1'>open conformation</scene> of NF1. The mechanism is shown in figure 1 and displays the slow hydrolysis of GTP bound to Ras and the fast hydrolysis of GTP when bound to NF1.
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<scene name='90/904311/Zinc_bound/1'>Zinc bound</scene>
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==Structure==
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NF1 is a protein dimer that exists in a <scene name='90/904311/Closed_conformation/1'>closed</scene> and <scene name='90/904311/Open_conformation/1'>open</scene> conformation. Each protomer contains a GRD, Sec14-PH, and a Gpex domain located on a HEAT N-C arm. Ras binds to the GRD site with Arg1276 being the critical residue for binding.
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<scene name='90/904311/Zinc_binding_site/2'>zinc binding site</scene>
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===Closed conformation===
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In the <scene name='90/904311/Closed_conformation/1'>closed conformation</scene>, one protomer has its domains shifted due to a 130 degree rotation. That rotation places <scene name='90/904312/Closed_arg/1'>Arg1276 in closed conformation</scene> in an orientation that <scene name='90/904312/Closed_zoom/1'>sterical hinders the binding between Ras and Arg1276</scene> in the GRD site (Figure 3). Making <scene name='90/904312/Closed_with_ras/1'>Ras binding in closed conformation</scene> sterically impossible in the <scene name='90/904311/Closed_conformation/1'>closed conformation</scene>
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<scene name='90/904312/Ras_bound_to_open_confirmation/1'>'Ras Bound to Open Confirmation'</scene>
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. The <scene name='90/904311/Closed_conformation/1'>closed conformation</scene> can exist naturally without any form of stabilization but will also fall back to the <scene name='90/904311/Open_conformation/1'>open conformation</scene>.
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<scene name='90/904312/Closed_confirmation_w_no_ras/1'>'Closed Confirmation with No Ras Bound'</scene>
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====Zinc Stabilized====
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The <scene name='90/904311/Closed_conformation/1'>closed conformation</scene> of NF1 can be stabilized by a zinc ion to prevent the shift back to an <scene name='90/904311/Open_conformation/1'>open conformation</scene>. This binding is done between C1032, H1558, and H1576 within the N-HEAT domain, GRD-Sec14-PH linker L2 and is shown in figure 2. When zinc stabilizes, NF1 will stay in the <scene name='90/904311/Closed_conformation/1'>closed conformation</scene> and continue to inhibit the binding of RAS.
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<scene name='90/904312/Closed_with_ras/1'>'Closed with Ras'</scene>
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===Open conformation===
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In the <scene name='90/904311/Open_conformation/1'>open conformation</scene> one protomer is shifted due to a 90 rotation. This rotation allows for binding between RAS and the <scene name='90/904312/Arg_1276_open/10'>Arg1276</scene>
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<scene name='90/904312/Sped-1_closed/7'>'SPRED-1 Bound to Closed'</scene>
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in the GRD site while in the <scene name='90/904311/Open_conformation/1'>open conformation</scene>. This means that the <scene name='90/904312/Arg_1276_open/11'>Arg1276 interaction with Ras in the open conformation</scene> can occur without any steric hindrance as shown in the <scene name='90/904311/Closed_conformation/1'>closed conformation</scene>.
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===Conformational Change Linkers===
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<scene name='90/904312/Spred-1_open/1'>'SPRED-1 Open'</scene>
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===Domains===
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===Arginine 1276===
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<scene name='90/904312/Arg_1276_open/10'>'ARG 1276 Open'</scene> <scene name='90/904312/Arg_1276_open/11'>'Zoomed'</scene>
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===Conformational Change Linkers===
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<scene name='90/904312/Closed_arg/1'>'Closed Arg'</scene><scene name='90/904312/Closed_zoom/1'>'Closed Zoom'</scene>
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<scene name='90/904312/Linker_closed/1'>''Linkers Closed'</scene><scene name='90/904312/Linker_closed/2'>'Zoomed LC'</scene>
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<scene name='90/904312/Linkers_open/2'>'Linkers Open'</scene><scene name='90/904312/Zoomed_lo/1'>'Zoomed LO'</scene>
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== Function ==
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== Disease ==
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== Relevance ==
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== Structural highlights ==
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This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.
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</StructureSection>
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== References ==
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<references/>
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Revision as of 20:59, 28 March 2022

This Sandbox is Reserved from February 28 through September 1, 2022 for use in the course CH462 Biochemistry II taught by R. Jeremy Johnson at the Butler University, Indianapolis, USA. This reservation includes Sandbox Reserved 1700 through Sandbox Reserved 1729.
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NF1 Closed Confirmation 7PGR

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