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Slack / Private Message Drop, p.327 [SLACK_000541] · slack_pm:msg:03444

Page text: p.327 · original PDF

Date: 2020-12-20 07:59
Type: chat message · slack
mentioned: Robert F. Garry
recipient: Kristian G. Andersen, Robert F. Garry, Edward C. Holmes
speaker: Andrew Rambaut

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@Robert Garry I don't think 501Y turns up in mink.

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2020-12-20 07:28 Robert F. Garry open

https://www.biorxiv.org/content/10.1101/2020.11.16.384743v1.full.pdf A couple of initial thoughts on the RBD changes. First, just to reiterate the dirty little "secret" of structural biologists - everything including cryoEM and X-raycrystallography are models - the resolutions are average and locally there is a lot of "fitting." That being said this figure from the Bullocks mink paper shows the residues in question E484 not to far from f486 obviously. Remarkable that N501 shows up in both the mink and the mouse. [shared file(s): image.png]
2020-12-20 07:28 Robert F. Garry open

https://www.nature.com/articles/s41586-020-2772-0
2020-12-20 07:54 Robert F. Garry open

Benton et al. is going to be the key to interpreting the NTD deletions and probably the other elephant mutations aswell. A pretty good interpretation of D614G therein. More importantly it clear that *both* NTD and the RBD need toundergo dramatic shifts that are driven by ACE2 binding to accommodate the S1/S2 and S2' cleavages and ultimately the large scale rearrangement of S2 into the 6 helix bundle. This doesn't rule out an NTD "receptor." Ineed to get to the office to look at the structures in Benton in a bit more detail to see what del69-70 etc do to theBenton structures, but it won't surprise me if they don't "destabilize" the trimer ala Doug.
2020-12-20 07:59 Andrew Rambaut

@Robert Garry I don't think 501Y turns up in mink.
2020-12-20 08:12 Robert F. Garry open

@Robert Garry It's N501T
2020-12-20 08:15 Robert F. Garry open

@Robert Garry Same residue changes to two diff amino acids when SC2 "adapts" to two diff animals.
2020-12-20 08:27 Robert F. Garry open

@Robert Garry In SC1 it's T501 fwiw.
2020-12-20 08:33 Robert F. Garry open

Note to self that the Benton structures are "stabilized" with two proline substitutions - this is what we did to ultimately get the Lassa GP structure.

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