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bioRxiv · 10.1101/2023.11.22.568381

Enhanced surface accessibility of SARS-CoV-2 Omicron spike protein due to an altered glycosylation profile

Wang, D.·Zhang, Z.·Baudys, J.·Haynes, C. A.·Osman, S. H.·Zhou, B.·Barr, J. R.·Gumbart, J. C.
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Abstract

SARS-CoV-2 spike (S) proteins undergo extensive glycosylation, aiding proper folding, enhancing stability, and evading host immune surveillance. In this study, we used mass spectrometric analysis to elucidate the N-glycosylation characteristics and disulfide bonding of recombinant spike proteins derived from the SARS-CoV-2 Omicron variant (B.1.1.529) in comparison with the D614G spike variant. Furthermore, we conducted microsecond-long molecular dynamics simulations on spike proteins to resolve how the different N-glycans impact spike conformational sampling in the two variants. Our findings reveal that the Omicron spike protein maintains an overall resemblance to the D614G spike variant in terms of site-specific glycan processing and disulfide bond formation. Nonetheless, alterations in glycans were observed at certain N-glycosylation sites. These changes, in synergy with mutations within the Omicron spike protein, result in increased surface accessibility of the macromolecule, including ectodomain, receptor-binding domain, and N-terminal domain. These insights contribute to our understanding of the interplay between structure and function, thereby advancing effective vaccination and therapeutic strategies. TeaserThrough mass spectrometry and molecular dynamics simulations, SARS-CoV-2 Omicron spike is found to be less covered by glycans when compared to the D614G spike variant.

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Wang, D., Zhang, Z., Baudys, J., Haynes, C. A., Osman, S. H., Zhou, B., Barr, J. R., Gumbart, J. C.. 2023-11-23. Enhanced surface accessibility of SARS-CoV-2 Omicron spike protein due to an altered glycosylation profile. https://doi.org/10.1101/2023.11.22.568381

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