I am super excited to let you know that our paper "Variations within the glycan shield of SARS-CoV-2 impact viral spike dynamics" in collaboration with Max Crispin's lab is now live on JMB #glycotime #SarsCoV2 #viralinfection #variants
#tootorial 🧵 ⬇️
https://www.sciencedirect.com/science/article/pii/S0022283622005551#f0030
The glycan shield covering the surface of the SARS-CoV-2 spike (S) protein is not only essential for immune evasion, but it's also functional, supporting S opening and thus viral infection.
Because of its functional role, the glycan shield is also subject to change under evolutionary pressure, something we have seen in the past (Harbison et al Chem Sci https://doi.org/10.1039/D1SC04832E) and recently in the gamma variant (P.1), as we discuss in this work
The dense glycan shield is an essential feature of the SARS-CoV-2 spike (S) architecture, key to immune evasion and to the activation of the prefusion conformation. Recent studies indicate that the occupancy and structures of the SARS-CoV-2 S glycans depend not only on the nature of the host cell, but also o
In this set the P.1 (Gamma) that spread through Brazil in July 2020 quickly replacing beta, carries *two* very interesting changes of its S glycan shield,
At N188 in the NTD there's a new sequon introduced by the R190S mutation,
N20 (T20N mutation) also in the NTD, which replaces the N17 in other VoCs as preferred site
Note, the changes in the glycan shield are the most significant changes relative to the beta variant ⬇️
As determined by glycoproteomics, the site at N188 carries an immature oligomannose, mostly a Man5, which is quite peculiar for the location, something we investigated with extensive MD simulations.
We discovered that the Man5 3 arm can occupy a pocket in the NTD, preventing its further functionalisation in the the Golgi
As an interesting insight this same pocket can be occupied in other variants by heme metabolites, such as biliverdin and bilirubin (DOI: 10.1126/sciadv.abg7607
4,557)
Binding of these metabolites keeps the NTD pocket open with implications in immune evasion due to changes in the conformation of the loop 183 to 187, which has been shown to be targeted by a novel polyclonal Ab.
Our simulations show that the presence of the Man5 at N188 is able to open the pocket, which otherwise would collapse due to the removal of a salt bridge cause by the R190S mutation, in a similar manner to heme metabolites.
Based on this, we propose that the introduction of a glycan at N188 could function as a permanent prop, opening the pocket and enhancing immune evasion.
Fin 😊
Last but not least, super congrats to all authors, and especially to,
*Maddie Newby* in Max's lab for the titanic work on the protein expression and glycoprotemics analysis 👏 👏 👏 🤩 🤩
and to,
*Carl Fogarty* in my lab who build the S glycoproteins and ran all the very complex simulations of the gamma in triplicates, with different orientations and presence/absence of glycosylation at N188 👏 👏 👏 🤩 🤩
Damn, the graphics are almost as beautiful as Christmas candy!
Congratulations on the paper! ( Do you know if the R code to make the plots is available?)
@folfdk Thank you!! Wasn't made for xmas, but it definitely matches the season 😂
I think I made the graphs with seaborn, but either or, we can send you everything no problem, just send me an email 😊👍
Chris Oostenbrink
Elisa Fadda-🔺
Folmer
GirtBySea