Sandbox Reserved 1706: Difference between revisions

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====Conformational Change Linkers====
====Conformational Change Linkers====
These three helical linkers (L1, L2, and L3) undergo rotations to relocate the GRD and Sec14-PH sites. Linker 1 (L1) consists of a loop connected by two helices from L1173-M1215 and is the main contributor in rotation of the GRD domain. The rotation of L1 to the <scene name='90/904311/Linkers_open/2'>Linkers in the Open Conformation</scene>
These three helical linkers (L1, L2, and L3) undergo rotations to relocate the GRD and Sec14-PH sites. Linker 1 (L1) consists of a loop connected by two helices from L1173-M1215 and is the main contributor in rotation of the GRD domain. The rotation of L1 to the open conformation causes N-HEAT ARM [https://en.wikipedia.org/wiki/Alpha_helix α helix] 48 and GRD helix 49 to extend out, aligning to form a hinge point at G1190. The GRD relocation is assisted by Sec14-PH relocation, which is initiated by Linker 3(L3) from Q1835 to G1852. Movement of L3 is further supported by rearrangement of the proline rich section of the C-HEAT ARM. L1 and L3 also move closer to each other in the open conformation initiating rearrangement of the GRD and Sec14-PH domain. Linker 2 (L2) consists of residues G1547-T1565 and begins at helix 63, the final helix of the GRD site, and connects into the short loop of [https://en.wikipedia.org/wiki/Alpha_helix α helix] 65 of the Sec14-PH domain and also assists in shifting the Sec14-PH away from the GRD site. The combination of these three linkers are largely responsible for the conformational shift of the <scene name='90/904311/Linker_closed/4'>closed conformation</scene>
<jmol>
  <jmolButton>
    <script>moveto 1.0 { -93 -976 -198 100.01} 317.4 0.0 0.0 {364.4077734377054 341.9358671885079 392.3046403678749} 146.92471247967674 {0 0 0} 0 0 0 3.0 0.0 0.0 </script> <text>🔎Zoom In(Closed Linkers)</text>
  </jmolButton>
</jmol> and <scene name='90/904311/Linkers_open/2'>open conformation</scene>
<jmol>
<jmol>
   <jmolButton>
   <jmolButton>
     <script>moveto 1.0 { 258 942 215 149.04} 254.03 0.0 0.0 {363.6198596926281 345.1996488441136 383.09000113650916} 143.7868028412415 {0 0 0} 0 0 0 3.0 0.0 0.0 </script> <text>🔎Zoom in</text>
     <script>moveto 1.0 { 258 942 215 149.04} 254.03 0.0 0.0 {363.6198596926281 345.1996488441136 383.09000113650916} 143.7868028412415 {0 0 0} 0 0 0 3.0 0.0 0.0 </script> <text>🔎Zoom in</text>
   </jmolButton>
   </jmolButton>
</jmol>  causes N-HEAT ARM [https://en.wikipedia.org/wiki/Alpha_helix α helix] 48 and GRD helix 49 to extend out, aligning to form a hinge point at G1190. The GRD relocation is assisted by Sec14-PH relocation, which is initiated by Linker 3(L3) from Q1835 to G1852. Movement of L3 is further supported by rearrangement of the proline rich section of the C-HEAT ARM. L1 and L3 also move closer to each other in the <scene name='90/904311/Linkers_open/1'>open conformation</scene> initiating rearrangement of the GRD and Sec14-PH domain. Linker 2 (L2) consists of residues G1547-T1565 and begins at helix 63, the final helix of the GRD site, and connects into the short loop of [https://en.wikipedia.org/wiki/Alpha_helix α helix] 65 of the Sec14-PH domain and also assists in shifting the Sec14-PH away from the GRD site. The combination of these three linkers are largely responsible for the conformational shift of the <scene name='90/904311/Linker_closed/1'> closed conformation</scene>
</jmol>.<ref name="Lupton"> DOI:10.1038/s41594-021-00687-2</ref><ref name="Naschberger"> DOI:10.1038/s41586-021-04024-x</ref>
<scene name='90/904312/Linker_closed/2'>(zoomed in)'</scene> and <scene name='90/904311/Linkers_open/1'>open conformation</scene>
<scene name='90/904312/Zoomed_lo/1'>(zoomed in)'</scene>.<ref name="Lupton"> DOI:10.1038/s41594-021-00687-2</ref><ref name="Naschberger"> DOI:10.1038/s41586-021-04024-x</ref>


==Ras Binding==
==Ras Binding==
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Closed Linker-
Closed Linker-
<scene name='90/904311/Linker_closed/4'>Linkers in Closed Conformation</scene>
<scene name='90/904311/Linker_closed/4'>Linkers in Closed Conformation</scene>
Button for closed zoomed in linkers"
<jmol>
<jmol>
   <jmolButton>
   <jmolButton>
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<scene name='90/904311/Arg_1276_open/14'>Arg 1276 w open zoomed out but with no Arg labeled</scene>
<scene name='90/904311/Arg_1276_open/14'>Arg 1276 w open zoomed out but with no Arg labeled</scene>
Button for open zoomed in Arg 1276"
<jmol>
<jmol>
   <jmolButton>
   <jmolButton>
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Open Zoomed out Molecular Interactions:
Open Zoomed out Molecular Interactions:
<scene name='90/904311/Arg_1276_mi/2'>Molecular Interaction Open</scene>
<scene name='90/904311/Arg_1276_mi/2'>Molecular Interaction Open</scene>
Button for open zoomed in Arg Molecular Interactions
<jmol>
<jmol>
   <jmolButton>
   <jmolButton>
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<scene name='90/904311/Closed_arg/6'>Molecular Interactions R1276 Closed</scene>
<scene name='90/904311/Closed_arg/6'>Molecular Interactions R1276 Closed</scene>
Button for molecular interactions closed R1276, E31, Y32
<jmol>
<jmol>
   <jmolButton>
   <jmolButton>
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