The effect of N-glycosylation of SARS-CoV-2 spike protein on the virus interaction with the host cell ACE2 receptor

Summary: The densely glycosylated spike (S) protein highly exposed on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) surface mediates host cell entry by binding to the receptor angiotensin-converting enzyme 2 (ACE2). However, the role of glycosylation has not been fully understood. In...

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Autores principales: Chuncui Huang, Zeshun Tan, Keli Zhao, Wenjun Zou, Hui Wang, Huanyu Gao, Shiwei Sun, Dongbo Bu, Wengang Chai, Yan Li
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Publicado: Elsevier 2021
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spelling oai:doaj.org-article:2d0562f6489549838ba1b3d9e2be89f32021-11-20T05:09:08ZThe effect of N-glycosylation of SARS-CoV-2 spike protein on the virus interaction with the host cell ACE2 receptor2589-004210.1016/j.isci.2021.103272https://doaj.org/article/2d0562f6489549838ba1b3d9e2be89f32021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221012414https://doaj.org/toc/2589-0042Summary: The densely glycosylated spike (S) protein highly exposed on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) surface mediates host cell entry by binding to the receptor angiotensin-converting enzyme 2 (ACE2). However, the role of glycosylation has not been fully understood. In this study, we investigated the effect of different N-glycosylation of S1 protein on its binding to ACE2. Using real-time surface plasmon resonance assay the negative effects were demonstrated by the considerable increase of binding affinities of de-N-glycosylated S1 proteins produced from three different expression systems including baculovirus-insect, Chinese hamster ovarian and two variants of human embryonic kidney 293 cells. Molecular dynamic simulations of the S1 protein-ACE2 receptor complex revealed the steric hindrance and Coulombic repulsion effects of different types of N-glycans on the S1 protein interaction with ACE2. The results should contribute to future pathological studies of SARS-CoV-2 and therapeutic development of Covid-19, particularly using recombinant S1 proteins as models.Chuncui HuangZeshun TanKeli ZhaoWenjun ZouHui WangHuanyu GaoShiwei SunDongbo BuWengang ChaiYan LiElsevierarticleProteinVirologyStructural biologyComputer simulationScienceQENiScience, Vol 24, Iss 11, Pp 103272- (2021)
institution DOAJ
collection DOAJ
language EN
topic Protein
Virology
Structural biology
Computer simulation
Science
Q
spellingShingle Protein
Virology
Structural biology
Computer simulation
Science
Q
Chuncui Huang
Zeshun Tan
Keli Zhao
Wenjun Zou
Hui Wang
Huanyu Gao
Shiwei Sun
Dongbo Bu
Wengang Chai
Yan Li
The effect of N-glycosylation of SARS-CoV-2 spike protein on the virus interaction with the host cell ACE2 receptor
description Summary: The densely glycosylated spike (S) protein highly exposed on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) surface mediates host cell entry by binding to the receptor angiotensin-converting enzyme 2 (ACE2). However, the role of glycosylation has not been fully understood. In this study, we investigated the effect of different N-glycosylation of S1 protein on its binding to ACE2. Using real-time surface plasmon resonance assay the negative effects were demonstrated by the considerable increase of binding affinities of de-N-glycosylated S1 proteins produced from three different expression systems including baculovirus-insect, Chinese hamster ovarian and two variants of human embryonic kidney 293 cells. Molecular dynamic simulations of the S1 protein-ACE2 receptor complex revealed the steric hindrance and Coulombic repulsion effects of different types of N-glycans on the S1 protein interaction with ACE2. The results should contribute to future pathological studies of SARS-CoV-2 and therapeutic development of Covid-19, particularly using recombinant S1 proteins as models.
format article
author Chuncui Huang
Zeshun Tan
Keli Zhao
Wenjun Zou
Hui Wang
Huanyu Gao
Shiwei Sun
Dongbo Bu
Wengang Chai
Yan Li
author_facet Chuncui Huang
Zeshun Tan
Keli Zhao
Wenjun Zou
Hui Wang
Huanyu Gao
Shiwei Sun
Dongbo Bu
Wengang Chai
Yan Li
author_sort Chuncui Huang
title The effect of N-glycosylation of SARS-CoV-2 spike protein on the virus interaction with the host cell ACE2 receptor
title_short The effect of N-glycosylation of SARS-CoV-2 spike protein on the virus interaction with the host cell ACE2 receptor
title_full The effect of N-glycosylation of SARS-CoV-2 spike protein on the virus interaction with the host cell ACE2 receptor
title_fullStr The effect of N-glycosylation of SARS-CoV-2 spike protein on the virus interaction with the host cell ACE2 receptor
title_full_unstemmed The effect of N-glycosylation of SARS-CoV-2 spike protein on the virus interaction with the host cell ACE2 receptor
title_sort effect of n-glycosylation of sars-cov-2 spike protein on the virus interaction with the host cell ace2 receptor
publisher Elsevier
publishDate 2021
url https://doaj.org/article/2d0562f6489549838ba1b3d9e2be89f3
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