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ACE2 N-glycosylation modulates interactions with SARS-CoV-2 spike protein in a site-specific manner
SARS-CoV-2 has evolved continuously and accumulated spike mutations with each variant having a different binding for the cellular ACE2 receptor. It is not known whether the interactions between such mutated spikes and ACE2 glycans are conserved among different variant lineages. Here, we focused on t...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9637154/ https://www.ncbi.nlm.nih.gov/pubmed/36335195 http://dx.doi.org/10.1038/s42003-022-04170-6 |
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author | Isobe, Ayana Arai, Yasuha Kuroda, Daisuke Okumura, Nobuaki Ono, Takao Ushiba, Shota Nakakita, Shin-ichi Daidoji, Tomo Suzuki, Yasuo Nakaya, Takaaki Matsumoto, Kazuhiko Watanabe, Yohei |
author_facet | Isobe, Ayana Arai, Yasuha Kuroda, Daisuke Okumura, Nobuaki Ono, Takao Ushiba, Shota Nakakita, Shin-ichi Daidoji, Tomo Suzuki, Yasuo Nakaya, Takaaki Matsumoto, Kazuhiko Watanabe, Yohei |
author_sort | Isobe, Ayana |
collection | PubMed |
description | SARS-CoV-2 has evolved continuously and accumulated spike mutations with each variant having a different binding for the cellular ACE2 receptor. It is not known whether the interactions between such mutated spikes and ACE2 glycans are conserved among different variant lineages. Here, we focused on three ACE2 glycosylation sites (53, 90 and 322) that are geometrically close to spike binding sites and investigated the effect of their glycosylation pattern on spike affinity. These glycosylation deletions caused distinct site-specific changes in interactions with the spike and acted cooperatively. Of note, the particular interaction profiles were conserved between the SARS-CoV-2 parental virus and the variants of concern (VOCs) Delta and Omicron. Our study provides insights for a better understanding of the importance of ACE2 glycosylation on ACE2/SARS-CoV-2 spike interaction and guidance for further optimization of soluble ACE2 for therapeutic use. |
format | Online Article Text |
id | pubmed-9637154 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-96371542022-11-07 ACE2 N-glycosylation modulates interactions with SARS-CoV-2 spike protein in a site-specific manner Isobe, Ayana Arai, Yasuha Kuroda, Daisuke Okumura, Nobuaki Ono, Takao Ushiba, Shota Nakakita, Shin-ichi Daidoji, Tomo Suzuki, Yasuo Nakaya, Takaaki Matsumoto, Kazuhiko Watanabe, Yohei Commun Biol Article SARS-CoV-2 has evolved continuously and accumulated spike mutations with each variant having a different binding for the cellular ACE2 receptor. It is not known whether the interactions between such mutated spikes and ACE2 glycans are conserved among different variant lineages. Here, we focused on three ACE2 glycosylation sites (53, 90 and 322) that are geometrically close to spike binding sites and investigated the effect of their glycosylation pattern on spike affinity. These glycosylation deletions caused distinct site-specific changes in interactions with the spike and acted cooperatively. Of note, the particular interaction profiles were conserved between the SARS-CoV-2 parental virus and the variants of concern (VOCs) Delta and Omicron. Our study provides insights for a better understanding of the importance of ACE2 glycosylation on ACE2/SARS-CoV-2 spike interaction and guidance for further optimization of soluble ACE2 for therapeutic use. Nature Publishing Group UK 2022-11-05 /pmc/articles/PMC9637154/ /pubmed/36335195 http://dx.doi.org/10.1038/s42003-022-04170-6 Text en © The Author(s) 2022 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Isobe, Ayana Arai, Yasuha Kuroda, Daisuke Okumura, Nobuaki Ono, Takao Ushiba, Shota Nakakita, Shin-ichi Daidoji, Tomo Suzuki, Yasuo Nakaya, Takaaki Matsumoto, Kazuhiko Watanabe, Yohei ACE2 N-glycosylation modulates interactions with SARS-CoV-2 spike protein in a site-specific manner |
title | ACE2 N-glycosylation modulates interactions with SARS-CoV-2 spike protein in a site-specific manner |
title_full | ACE2 N-glycosylation modulates interactions with SARS-CoV-2 spike protein in a site-specific manner |
title_fullStr | ACE2 N-glycosylation modulates interactions with SARS-CoV-2 spike protein in a site-specific manner |
title_full_unstemmed | ACE2 N-glycosylation modulates interactions with SARS-CoV-2 spike protein in a site-specific manner |
title_short | ACE2 N-glycosylation modulates interactions with SARS-CoV-2 spike protein in a site-specific manner |
title_sort | ace2 n-glycosylation modulates interactions with sars-cov-2 spike protein in a site-specific manner |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9637154/ https://www.ncbi.nlm.nih.gov/pubmed/36335195 http://dx.doi.org/10.1038/s42003-022-04170-6 |
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