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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American
Chemical Society
2021
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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 |
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author | 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 |
author_facet | 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 |
author_sort | Allen, Joel D. |
collection | PubMed |
description | [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. |
format | Online Article Text |
id | pubmed-8262170 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American
Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-82621702021-07-08 Site-Specific Steric Control of SARS-CoV-2 Spike Glycosylation 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 Biochemistry [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. American Chemical Society 2021-07-02 2021-07-13 /pmc/articles/PMC8262170/ /pubmed/34213308 http://dx.doi.org/10.1021/acs.biochem.1c00279 Text en © 2021 The Authors. Published by American Chemical Society Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | 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 Site-Specific Steric Control of SARS-CoV-2 Spike Glycosylation |
title | Site-Specific Steric Control of SARS-CoV-2
Spike Glycosylation |
title_full | Site-Specific Steric Control of SARS-CoV-2
Spike Glycosylation |
title_fullStr | Site-Specific Steric Control of SARS-CoV-2
Spike Glycosylation |
title_full_unstemmed | Site-Specific Steric Control of SARS-CoV-2
Spike Glycosylation |
title_short | Site-Specific Steric Control of SARS-CoV-2
Spike Glycosylation |
title_sort | site-specific steric control of sars-cov-2
spike glycosylation |
url | 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 |
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