Newby, Maddy L. and Fogarty, Carl A. and Allen, Joel D. and Butler, John and Fadda, Elisa and Crispin, Max
(2023)
Variations within the Glycan Shield of SARS-CoV-2 Impact Viral Spike Dynamics.
Journal of Molecular Biology, 435 (4).
p. 167928.
ISSN 0022-2836
Abstract
The emergence of SARS-CoV-2 variants alters the efficacy of existing immunity, whether arisen naturally
or through vaccination. Understanding the structure of the viral spike assists in determining the impact of
mutations on the antigenic surface. One class of mutation impacts glycosylation attachment sites, which
have the capacity to influence the antigenic structure beyond the immediate site of attachment. Here, we
compare the site-specific glycosylation of recombinant viral spike mimetics of B.1.351 (Beta), P.1
(Gamma), B.1.617.2 (Delta), B.1.1.529 (Omicron). The P.1 strain exhibits two additional N-linked glycan
sites compared to the other variants analyzed and we investigate the impact of these glycans by molec-
ular dynamics. The acquired N188 site is shown to exhibit very limited glycan maturation, consistent with
limited enzyme accessibility. Structural modeling and molecular dynamics reveal that N188 is located
within a cavity by the receptor binding domain, which influences the dynamics of these attachment
domains. These observations suggest a mechanism whereby mutations affecting viral glycosylation sites
have a structural impact across the protein surface.
| Item Type: |
Article
|
| Keywords: |
SARS-CoV-2;
glycosylation;
variant of concern;
mass spectrometry;
molecular dynamics; |
| Academic Unit: |
Faculty of Science and Engineering > Chemistry |
| Item ID: |
16958 |
| Identification Number: |
https://doi.org/10.1016/j.jmb.2022.167928 |
| Depositing User: |
Elisa Fadda
|
| Date Deposited: |
21 Feb 2023 14:31 |
| Journal or Publication Title: |
Journal of Molecular Biology |
| Publisher: |
Elsevier |
| Refereed: |
Yes |
| URI: |
|
| Use Licence: |
This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available
here |
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