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Site-specific steric control of SARS-CoV-2 spike glycosylation

Site-specific steric control of SARS-CoV-2 spike glycosylation
Site-specific steric control of SARS-CoV-2 spike glycosylation

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.

Animals, COVID-19 Vaccines/genetics, COVID-19/genetics, Chlorocebus aethiops, Glycosylation, Humans, Molecular Dynamics Simulation, Protein Binding/genetics, Protein Conformation, SARS-CoV-2/genetics, Spike Glycoprotein, Coronavirus/chemistry, Vero Cells
0006-2960
2153-2169
Allen, Joel D
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Chawla, Himanshi
07b9e983-4c35-4314-999d-fe3222a6c03b
Zuzic, Lorena
605be3bf-30ba-47cb-83be-bfdcd1bb1952
Shivgan, Aishwary Tukaram
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Watanabe, Yasunori
8c0ee4af-a293-4de5-9036-3ce2051b380c
He, Wan-Ting
c532ea3d-67d9-4791-a3a8-3eec756f19c2
Callaghan, Sean
d1541a40-ae1b-49a8-8310-08681bdab1ab
Song, Ge
be91c0bc-98ce-40e4-af78-41547b440644
Yong, Peter
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Brouwer, Philip J M
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Song, Yutong
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Cai, Yongfei
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Duyvesteyn, Helen M E
c883b328-4c22-4516-b818-66cc5793b432
Malinauskas, Tomas
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Kint, Joeri
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Pino, Paco
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Wurm, Maria J
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Frank, Martin
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Chen, Bing
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Stuart, David I
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Sanders, Rogier W
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Andrabi, Raiees
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Burton, Dennis R
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Li, Sai
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Bond, Peter J
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Crispin, Max
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Allen, Joel D
c89d5569-7659-4835-b535-c9586e956b3a
Chawla, Himanshi
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Zuzic, Lorena
605be3bf-30ba-47cb-83be-bfdcd1bb1952
Shivgan, Aishwary Tukaram
0ae6d969-37c0-4f69-a01a-4a82391474df
Watanabe, Yasunori
8c0ee4af-a293-4de5-9036-3ce2051b380c
He, Wan-Ting
c532ea3d-67d9-4791-a3a8-3eec756f19c2
Callaghan, Sean
d1541a40-ae1b-49a8-8310-08681bdab1ab
Song, Ge
be91c0bc-98ce-40e4-af78-41547b440644
Yong, Peter
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Brouwer, Philip J M
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Song, Yutong
e40d4fb3-f448-4275-83c5-5dc3a423b7c5
Cai, Yongfei
004d523e-2b59-48bf-86c2-ac2fb8b36a45
Duyvesteyn, Helen M E
c883b328-4c22-4516-b818-66cc5793b432
Malinauskas, Tomas
3657258d-f3b3-4b93-a652-5b8ef40a7add
Kint, Joeri
2ed27807-87aa-4bec-baee-1d32e6569bbe
Pino, Paco
7c437aa7-8c23-40eb-bc50-60639f16b916
Wurm, Maria J
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Frank, Martin
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Chen, Bing
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Stuart, David I
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Sanders, Rogier W
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Andrabi, Raiees
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Burton, Dennis R
a628ce77-b694-4e3c-86a5-11f4e20e1c7c
Li, Sai
6d4fd055-1024-44be-872d-3c0f55b98edd
Bond, Peter J
08f46940-85e8-44c4-a368-d94342a10fd6
Crispin, Max
cd980957-0943-4b89-b2b2-710f01f33bc9

Allen, Joel D, Chawla, Himanshi, 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 and Crispin, Max (2021) Site-specific steric control of SARS-CoV-2 spike glycosylation. Biochemistry, 60 (27), 2153-2169. (doi:10.1021/acs.biochem.1c00279).

Record type: Article

Abstract

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.

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More information

Published date: 13 July 2021
Keywords: Animals, COVID-19 Vaccines/genetics, COVID-19/genetics, Chlorocebus aethiops, Glycosylation, Humans, Molecular Dynamics Simulation, Protein Binding/genetics, Protein Conformation, SARS-CoV-2/genetics, Spike Glycoprotein, Coronavirus/chemistry, Vero Cells
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Identifiers

Local EPrints ID: 450379
URI: http://eprints.soton.ac.uk/id/eprint/450379
DOI: doi:10.1021/acs.biochem.1c00279
ISSN: 0006-2960
PURE UUID: 4b4740f7-d947-4f0c-9e70-e3d57d687fba
ORCID for Joel D Allen: ORCID iD orcid.org/0000-0003-2547-968X
ORCID for Himanshi Chawla: ORCID iD orcid.org/0000-0001-9828-6593
ORCID for Max Crispin: ORCID iD orcid.org/0000-0002-1072-2694

Catalogue record

Date deposited: 26 Jul 2021 16:33
Last modified: 17 Mar 2024 04:09

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Contributors

Author: Joel D Allen ORCID iD
Author: Himanshi Chawla ORCID iD
Author: Lorena Zuzic
Author: Aishwary Tukaram Shivgan
Author: Yasunori Watanabe
Author: Wan-Ting He
Author: Sean Callaghan
Author: Ge Song
Author: Peter Yong
Author: Philip J M Brouwer
Author: Yutong Song
Author: Yongfei Cai
Author: Helen M E Duyvesteyn
Author: Tomas Malinauskas
Author: Joeri Kint
Author: Paco Pino
Author: Maria J Wurm
Author: Martin Frank
Author: Bing Chen
Author: David I Stuart
Author: Rogier W Sanders
Author: Raiees Andrabi
Author: Dennis R Burton
Author: Sai Li
Author: Peter J Bond
Author: Max Crispin ORCID iD

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