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Structural insights into the modulation of coronavirus spike tilting and infectivity by hinge glycans
Coronavirus spike glycoproteins presented on the virion surface mediate receptor binding, and membrane fusion during virus entry and constitute the primary target for vaccine and drug development. How the structure dynamics of the full-length spikes incorporated in viral lipid envelope correlates wi...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10630519/ https://www.ncbi.nlm.nih.gov/pubmed/37935678 http://dx.doi.org/10.1038/s41467-023-42836-9 |
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author | Chmielewski, David Wilson, Eric A. Pintilie, Grigore Zhao, Peng Chen, Muyuan Schmid, Michael F. Simmons, Graham Wells, Lance Jin, Jing Singharoy, Abhishek Chiu, Wah |
author_facet | Chmielewski, David Wilson, Eric A. Pintilie, Grigore Zhao, Peng Chen, Muyuan Schmid, Michael F. Simmons, Graham Wells, Lance Jin, Jing Singharoy, Abhishek Chiu, Wah |
author_sort | Chmielewski, David |
collection | PubMed |
description | Coronavirus spike glycoproteins presented on the virion surface mediate receptor binding, and membrane fusion during virus entry and constitute the primary target for vaccine and drug development. How the structure dynamics of the full-length spikes incorporated in viral lipid envelope correlates with the virus infectivity remains poorly understood. Here we present structures and distributions of native spike conformations on vitrified human coronavirus NL63 (HCoV-NL63) virions without chemical fixation by cryogenic electron tomography (cryoET) and subtomogram averaging, along with site-specific glycan composition and occupancy determined by mass spectrometry. The higher oligomannose glycan shield on HCoV-NL63 spikes than on SARS-CoV-2 spikes correlates with stronger immune evasion of HCoV-NL63. Incorporation of cryoET-derived native spike conformations into all-atom molecular dynamic simulations elucidate the conformational landscape of the glycosylated, full-length spike that reveals a role of hinge glycans in modulating spike bending. We show that glycosylation at N1242 at the upper portion of the stalk is responsible for the extensive orientational freedom of the spike crown. Subsequent infectivity assays implicated involvement of N1242-glyan in virus entry. Our results suggest a potential therapeutic target site for HCoV-NL63. |
format | Online Article Text |
id | pubmed-10630519 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-106305192023-11-07 Structural insights into the modulation of coronavirus spike tilting and infectivity by hinge glycans Chmielewski, David Wilson, Eric A. Pintilie, Grigore Zhao, Peng Chen, Muyuan Schmid, Michael F. Simmons, Graham Wells, Lance Jin, Jing Singharoy, Abhishek Chiu, Wah Nat Commun Article Coronavirus spike glycoproteins presented on the virion surface mediate receptor binding, and membrane fusion during virus entry and constitute the primary target for vaccine and drug development. How the structure dynamics of the full-length spikes incorporated in viral lipid envelope correlates with the virus infectivity remains poorly understood. Here we present structures and distributions of native spike conformations on vitrified human coronavirus NL63 (HCoV-NL63) virions without chemical fixation by cryogenic electron tomography (cryoET) and subtomogram averaging, along with site-specific glycan composition and occupancy determined by mass spectrometry. The higher oligomannose glycan shield on HCoV-NL63 spikes than on SARS-CoV-2 spikes correlates with stronger immune evasion of HCoV-NL63. Incorporation of cryoET-derived native spike conformations into all-atom molecular dynamic simulations elucidate the conformational landscape of the glycosylated, full-length spike that reveals a role of hinge glycans in modulating spike bending. We show that glycosylation at N1242 at the upper portion of the stalk is responsible for the extensive orientational freedom of the spike crown. Subsequent infectivity assays implicated involvement of N1242-glyan in virus entry. Our results suggest a potential therapeutic target site for HCoV-NL63. Nature Publishing Group UK 2023-11-07 /pmc/articles/PMC10630519/ /pubmed/37935678 http://dx.doi.org/10.1038/s41467-023-42836-9 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Chmielewski, David Wilson, Eric A. Pintilie, Grigore Zhao, Peng Chen, Muyuan Schmid, Michael F. Simmons, Graham Wells, Lance Jin, Jing Singharoy, Abhishek Chiu, Wah Structural insights into the modulation of coronavirus spike tilting and infectivity by hinge glycans |
title | Structural insights into the modulation of coronavirus spike tilting and infectivity by hinge glycans |
title_full | Structural insights into the modulation of coronavirus spike tilting and infectivity by hinge glycans |
title_fullStr | Structural insights into the modulation of coronavirus spike tilting and infectivity by hinge glycans |
title_full_unstemmed | Structural insights into the modulation of coronavirus spike tilting and infectivity by hinge glycans |
title_short | Structural insights into the modulation of coronavirus spike tilting and infectivity by hinge glycans |
title_sort | structural insights into the modulation of coronavirus spike tilting and infectivity by hinge glycans |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10630519/ https://www.ncbi.nlm.nih.gov/pubmed/37935678 http://dx.doi.org/10.1038/s41467-023-42836-9 |
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