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N501Y mutation of spike protein in SARS-CoV-2 strengthens its binding to receptor ACE2
SARS-CoV-2 has been spreading around the world for the past year. Recently, several variants such as B.1.1.7 (alpha), B.1.351 (beta), and P.1 (gamma), which share a key mutation N501Y on the receptor-binding domain (RBD), appear to be more infectious to humans. To understand the underlying mechanism...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455130/ https://www.ncbi.nlm.nih.gov/pubmed/34414884 http://dx.doi.org/10.7554/eLife.69091 |
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author | Tian, Fang Tong, Bei Sun, Liang Shi, Shengchao Zheng, Bin Wang, Zibin Dong, Xianchi Zheng, Peng |
author_facet | Tian, Fang Tong, Bei Sun, Liang Shi, Shengchao Zheng, Bin Wang, Zibin Dong, Xianchi Zheng, Peng |
author_sort | Tian, Fang |
collection | PubMed |
description | SARS-CoV-2 has been spreading around the world for the past year. Recently, several variants such as B.1.1.7 (alpha), B.1.351 (beta), and P.1 (gamma), which share a key mutation N501Y on the receptor-binding domain (RBD), appear to be more infectious to humans. To understand the underlying mechanism, we used a cell surface-binding assay, a kinetics study, a single-molecule technique, and a computational method to investigate the interaction between these RBD (mutations) and ACE2. Remarkably, RBD with the N501Y mutation exhibited a considerably stronger interaction, with a faster association rate and a slower dissociation rate. Atomic force microscopy (AFM)-based single-molecule force microscopy (SMFS) consistently quantified the interaction strength of RBD with the mutation as having increased binding probability and requiring increased unbinding force. Molecular dynamics simulations of RBD–ACE2 complexes indicated that the N501Y mutation introduced additional π-π and π-cation interactions that could explain the changes observed by force microscopy. Taken together, these results suggest that the reinforced RBD–ACE2 interaction that results from the N501Y mutation in the RBD should play an essential role in the higher rate of transmission of SARS-CoV-2 variants, and that future mutations in the RBD of the virus should be under surveillance. |
format | Online Article Text |
id | pubmed-8455130 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-84551302021-09-23 N501Y mutation of spike protein in SARS-CoV-2 strengthens its binding to receptor ACE2 Tian, Fang Tong, Bei Sun, Liang Shi, Shengchao Zheng, Bin Wang, Zibin Dong, Xianchi Zheng, Peng eLife Structural Biology and Molecular Biophysics SARS-CoV-2 has been spreading around the world for the past year. Recently, several variants such as B.1.1.7 (alpha), B.1.351 (beta), and P.1 (gamma), which share a key mutation N501Y on the receptor-binding domain (RBD), appear to be more infectious to humans. To understand the underlying mechanism, we used a cell surface-binding assay, a kinetics study, a single-molecule technique, and a computational method to investigate the interaction between these RBD (mutations) and ACE2. Remarkably, RBD with the N501Y mutation exhibited a considerably stronger interaction, with a faster association rate and a slower dissociation rate. Atomic force microscopy (AFM)-based single-molecule force microscopy (SMFS) consistently quantified the interaction strength of RBD with the mutation as having increased binding probability and requiring increased unbinding force. Molecular dynamics simulations of RBD–ACE2 complexes indicated that the N501Y mutation introduced additional π-π and π-cation interactions that could explain the changes observed by force microscopy. Taken together, these results suggest that the reinforced RBD–ACE2 interaction that results from the N501Y mutation in the RBD should play an essential role in the higher rate of transmission of SARS-CoV-2 variants, and that future mutations in the RBD of the virus should be under surveillance. eLife Sciences Publications, Ltd 2021-08-20 /pmc/articles/PMC8455130/ /pubmed/34414884 http://dx.doi.org/10.7554/eLife.69091 Text en © 2021, Tian et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Structural Biology and Molecular Biophysics Tian, Fang Tong, Bei Sun, Liang Shi, Shengchao Zheng, Bin Wang, Zibin Dong, Xianchi Zheng, Peng N501Y mutation of spike protein in SARS-CoV-2 strengthens its binding to receptor ACE2 |
title | N501Y mutation of spike protein in SARS-CoV-2 strengthens its binding to receptor ACE2 |
title_full | N501Y mutation of spike protein in SARS-CoV-2 strengthens its binding to receptor ACE2 |
title_fullStr | N501Y mutation of spike protein in SARS-CoV-2 strengthens its binding to receptor ACE2 |
title_full_unstemmed | N501Y mutation of spike protein in SARS-CoV-2 strengthens its binding to receptor ACE2 |
title_short | N501Y mutation of spike protein in SARS-CoV-2 strengthens its binding to receptor ACE2 |
title_sort | n501y mutation of spike protein in sars-cov-2 strengthens its binding to receptor ace2 |
topic | Structural Biology and Molecular Biophysics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455130/ https://www.ncbi.nlm.nih.gov/pubmed/34414884 http://dx.doi.org/10.7554/eLife.69091 |
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