SARS-CoV-2 spike protein fusion transformation: Difference between revisions
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:(2) The virus membrane is attached near the <font color="red">'''red balls'''</font>. The <scene name='85/857791/Morf-6xr8-6xra-lin-theis-cao/7'>virus membrane appears to be pulled into close proximity to the host cell membrane</scene> (near the <font color="#0060ff">'''blue balls'''</font>), initiating membrane fusion. The virus membrane is brought closer than shown here: these models lack the stem. The <font color="red">'''red balls'''</font> would actually end up much closer to the <font color="#0060ff">'''blue balls'''</font> than these models show. | :(2) The virus membrane is attached near the <font color="red">'''red balls'''</font>. The <scene name='85/857791/Morf-6xr8-6xra-lin-theis-cao/7'>virus membrane appears to be pulled into close proximity to the host cell membrane</scene> (near the <font color="#0060ff">'''blue balls'''</font>), initiating membrane fusion. The virus membrane is brought closer than shown here: these models lack the stem. The <font color="red">'''red balls'''</font> would actually end up much closer to the <font color="#0060ff">'''blue balls'''</font> than these models show. | ||
<center><i>Use the '''toggle animation''' button to restart animation as needed.<br> | <center><i>Use the '''toggle animation''' button above to restart animation as needed.<br> | ||
Remember that a [[morph]] is intended to help you compare two structures. This morph does NOT portray a realistic transition pathway.</i></center> | Remember that a [[morph]] is intended to help you compare two structures. This morph does NOT portray a realistic transition pathway.</i></center> | ||
:(3) The <scene name='85/857791/Morf-6xr8-6xra-lin-theis-cao/8'>middle portion of the spike protein remains relatively stable</scene>. | :(3) The <scene name='85/857791/Morf-6xr8-6xra-lin-theis-cao/8'>middle portion of the spike protein remains relatively stable</scene>. | ||
An <jmol> | |||
<jmolLink> | |||
<script>load /images/0/09/Spike_SARS_CoV_2_storymorph.pdb; script /scripts/85/857791/Alternate_morph/1.spt; | |||
model 0; select protein and not (912,1162); backbone only; select all; backbone 0.8; | |||
select 912,1162; spacefill 4.0; | |||
anim on</script> | |||
<text>alternate pathway</text> | |||
</jmolLink> | |||
</jmol> <ref>The [[Jmol/Storymorph|Storymorph Jmol scripts]] were used to create the interpolation shown in the morph. [https://proteopedia.org/wiki/index.php/Image:Spike_SARS_CoV_2_storymorph.pdb|Coordinates] available on Proteopedia</ref> between the two conformations shows how some secondary structure is retained while structural elements change orientation and position substantially. USe the button above to start and pause the morph. | |||
<jmol> | |||
<jmolRadioGroup> | |||
<item> | |||
<script>model 0; select not (912, 1162); backbone only; backbone 0.8; model 1; anim on</script> | |||
<text>Lines</text> | |||
<checked>true</checked> | |||
</item> | |||
<item> | |||
<script>model 0; select not (912, 1162); spacefill only; spacefill 4.0; model 1; anim on</script> | |||
<text>Spheres</text> | |||
<checked>false</checked> | |||
</item> | |||
</jmolRadioGroup> | |||
</jmol> | |||
===Membrane Fusion Schematic=== | ===Membrane Fusion Schematic=== | ||
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===Molecular Dynamics Simulation of Membrane Fusion=== | ===Molecular Dynamics Simulation of Membrane Fusion=== | ||
Molecular dynamics simulations are consistent with this hypothesis. Below is shown a liposome containing influenza hemagglutinin fusing with a lipid bilayer in a molecular dynamics simulation<ref name="pabis" />. | [[Molecular dynamics simulations]] are consistent with this hypothesis. Below is shown a liposome containing influenza hemagglutinin fusing with a lipid bilayer in a molecular dynamics simulation<ref name="pabis" />. | ||
<table style="border-collapse:collapse;border:1px solid black;width:700px;"><tr><td> | <table style="border-collapse:collapse;border:1px solid black;width:700px;"><tr><td> | ||
[[Image:Pabis-MDS-Fig1AD-Labeled.jpg|700px]] | [[Image:Pabis-MDS-Fig1AD-Labeled.jpg|700px]] | ||
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'''[http://proteopedia.org/wiki/images/6/67/Spike_protein_fusion_mainchain_morph_from_Proteopedia.Org.gif Download] (right click, save link as)''' 500 px wide main chain animation. This shows a smoothed main chain (backbone) trace. Please credit '''Proteopedia.Org''' in accord with our [[Proteopedia:Terms of Service|license]], and '''Cai, Zhang and coworkers<ref name="cai-zhang" />''' for their cryo-EM structures.<br> | '''[http://proteopedia.org/wiki/images/6/67/Spike_protein_fusion_mainchain_morph_from_Proteopedia.Org.gif Download] (right click, save link as)''' 500 px wide main chain animation. This shows a smoothed main chain (backbone) trace. Please credit '''Proteopedia.Org''' in accord with our [[Proteopedia:Terms of Service|license]], and '''Cai, Zhang and coworkers<ref name="cai-zhang" />''' for their cryo-EM structures.<br> | ||
[[Image:Spike protein fusion mainchain morph from Proteopedia.Org.gif]] | [[Image:Spike protein fusion mainchain morph from Proteopedia.Org.gif]] | ||
===Alternate Pathway for Transformation=== | |||
Given that a [[morph]] is intended to help you compare two structures and does not portray a realistic transition pathway, there are many pathways we can imagine. Below is another one that has structural elements swing away from the core structure in a hinge motion as they change conformation. Another choice in this morph is to have different timings for the distinct changes to be able to follow them one at a time. | |||
In the morph at full resolution, you can see a large cavity disappearing, the beta sheets acquiring an additional strand from a different subunit (subunits shown in green, blue and red tints), and changes in the core helix bundle along with the formation of the coiled-coil protrusion made of three helices. | |||
'''[https://proteopedia.org/wiki/images/e/ef/Spike_storymorph.gif Download] (right click, save link as)''' 720 px wide main chain animation. This shows a smoothed main chain (backbone) trace. Please credit '''Proteopedia.Org''' in accord with our [[Proteopedia:Terms of Service|license]], and '''Cai, Zhang and coworkers<ref name="cai-zhang" />''' for their cryo-EM structures.<br> | |||
[[Image:Spike labeled small.gif]] | |||
'''[https://proteopedia.org/wiki/images/3/34/Spike_labeled_spacefill.gif Download] (right click, save link as)''' 720 px wide main chain animation. This shows C-alpha atoms as large spheres. Please credit '''Proteopedia.Org''' in accord with our [[Proteopedia:Terms of Service|license]], and '''Cai, Zhang and coworkers<ref name="cai-zhang" />''' for their cryo-EM structures.<br> | |||
[[Image:Spike labeled spacefill small.gif]] | |||
===Pre-Fusion Spike Protein=== | ===Pre-Fusion Spike Protein=== | ||
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==See Also== | ==See Also== | ||
*[[SARS-CoV-2 spike protein priming by furin]] - the step prior to membrane fusion. | *[[SARS-CoV-2 spike protein priming by furin]] - the step prior to membrane fusion. | ||
*[[SARS-CoV-2 spike protein mutations]] suspected to increase transmission rates. | |||
*[[SARS-CoV-2 protein S]] | *[[SARS-CoV-2 protein S]] | ||
*[[Spike protein]] | *[[Spike protein]] | ||
*[[Coronavirus Disease 2019 (COVID-19)]] | *[[Coronavirus Disease 2019 (COVID-19)]] | ||
*[[User:Andre Wu Le Chun/Sandbox 1|Prefusion 2019-nCoV spike glycoprotein with a single receptor-binding domain up]] about [[6vsb]] | *[[User:Andre Wu Le Chun/Sandbox 1|Prefusion 2019-nCoV spike glycoprotein with a single receptor-binding domain up]] about [[6vsb]] | ||
*[[Jmol/Cavities pockets and tunnels]] | |||
*[[Cavity programs]] | |||
==Methods== | ==Methods== | ||
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[[6zgi]] was loaded into the [[Jmol/Application|Jmol Java application]] (~11-fold faster than [[JSmol]]), and rendered as translucent backbone, each chain a different pastel color. The command | [[6zgi]] was loaded into the [[Jmol/Application|Jmol Java application]] (~11-fold faster than [[JSmol]]), and rendered as translucent backbone, each chain a different pastel color. The command | ||
:<tt>isosurface minset 100 interior cavity 3.0 10.0</tt> | :<tt>isosurface minset 100 interior cavity 3.0 10.0</tt> | ||
was executed (~45 sec). The numeric parameters in that command were determined by trial and error (see [[Jmol/Cavities pockets and tunnels]]). The cavity surface data were saved as Jmol voxel data, and uploaded to Proteopedia as [[Image:6zgi-cavities.jvxl]]. The button above reads that file to | was executed (~45 sec). The numeric parameters in that command were determined by trial and error (see [[Jmol/Cavities pockets and tunnels]]). The cavity surface data were saved as Jmol voxel data, and uploaded to Proteopedia as [[Image:6zgi-cavities.jvxl]]. The button above reads that file, rather than re-calculating the cavities, in order to display the interior cavity surface data much more quickly. See also [[Jmol/Cavities pockets and tunnels]]. | ||
==Acknowledgement== | |||
Eric Martz thanks Deborah Spitz for a critique that improved this article. | |||
== References and Notes == | == References and Notes == | ||
<references/> | <references/> | ||