Why 2 proline (P) substitutions will go down in history.
Introducing 2P's at the beginning of the central helix (CH) stabilized the spike protein's confirmation upon entering cells.
From the Jan 10 #SARSCoV2 sequence, this 2P Δ was incorporated into the mRNA vaccine designs /1
This was a result of elegant #3D structural biology work @NIH (Barney Graham), @scrippsresearch (Andrew Ward) and collaborators from a @PNASNews paper that was rejected 5 times! pnas.org/content/114/35… /2
Without the 2P design, the mRNA vaccines would have failed.
The remarkable story is told well by @Carolynyjohnson
washingtonpost.com/health/2020/12… /3
The @PBS video explanation is outstanding, by @DrJoeHanson with @McLellan_Lab @UTAustin key driver in this structural biology breakthrough /4
More on the spike protein's confirmation dynamics in this perspective on a new paper @cellhostmicrobe cell.com/cell-host-micr…
Original report cell.com/cell-host-micr…
Knowing how the spike protein changed confirmation upon cell membrane fusion was key (and how to Δ it), and the details were furthered by this recent work.
Extraordinary video of the spike protein in motion
w/great cover @oooitsplasma @ScienceMagazine /6
There are 4 #SARSCoV2 vaccines that incorporate the 2P design. Besides @moderna_tx @BioNTech_Group/Pfizer, @Novavax and @JNJNews. And thanks @goodwish916 @WardLab1 @KizzyPhD who I did not acknowledge earlier or didn't have their twitter handle
For an enthralling account of the 2P substitution and its big impact, you can listen or read the transcript thisamericanlife.org Starts at 40 min, with @goodwish916 @McLellan_Lab @KizzyPhD and Barney Graham @ThisAmerLife w/ @dkestenbaum
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