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Site-Specific Steric Control of SARS-CoV-2 Spike Glycosylation

[Image: see text] A central tenet in the design of vaccines is the display of native-like antigens in the elicitation of protective immunity. The abundance of N-linked glycans across the SARS-CoV-2 spike protein is a potential source of heterogeneity among the many different vaccine candidates under...

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Detalles Bibliográficos
Autores principales: Allen, Joel D., Chawla, Himanshi, Samsudin, Firdaus, Zuzic, Lorena, Shivgan, Aishwary Tukaram, Watanabe, Yasunori, He, Wan-ting, Callaghan, Sean, Song, Ge, Yong, Peter, Brouwer, Philip J. M., Song, Yutong, Cai, Yongfei, Duyvesteyn, Helen M. E., Malinauskas, Tomas, Kint, Joeri, Pino, Paco, Wurm, Maria J., Frank, Martin, Chen, Bing, Stuart, David I., Sanders, Rogier W., Andrabi, Raiees, Burton, Dennis R., Li, Sai, Bond, Peter J., Crispin, Max
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2021
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262170/
https://www.ncbi.nlm.nih.gov/pubmed/34213308
http://dx.doi.org/10.1021/acs.biochem.1c00279
Descripción
Sumario:[Image: see text] A central tenet in the design of vaccines is the display of native-like antigens in the elicitation of protective immunity. The abundance of N-linked glycans across the SARS-CoV-2 spike protein is a potential source of heterogeneity among the many different vaccine candidates under investigation. Here, we investigate the glycosylation of recombinant SARS-CoV-2 spike proteins from five different laboratories and compare them against S protein from infectious virus, cultured in Vero cells. We find patterns that are conserved across all samples, and this can be associated with site-specific stalling of glycan maturation that acts as a highly sensitive reporter of protein structure. Molecular dynamics simulations of a fully glycosylated spike support a model of steric restrictions that shape enzymatic processing of the glycans. These results suggest that recombinant spike-based SARS-CoV-2 immunogen glycosylation reproducibly recapitulates signatures of viral glycosylation.