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...

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Autores principales:	Fang Tian, Bei Tong, Liang Sun, Shengchao Shi, Bin Zheng, Zibin Wang, Xianchi Dong, Peng Zheng
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	SARS-CoV-2 spike protein single-molecule force spectroscopy MD simulations protein–protein interaction Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/6d6d325ec0514285a12b3deb6ab193f0
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spelling	oai:doaj.org-article:6d6d325ec0514285a12b3deb6ab193f02021-11-26T07:07:33ZN501Y mutation of spike protein in SARS-CoV-2 strengthens its binding to receptor ACE210.7554/eLife.690912050-084Xe69091https://doaj.org/article/6d6d325ec0514285a12b3deb6ab193f02021-08-01T00:00:00Zhttps://elifesciences.org/articles/69091https://doaj.org/toc/2050-084XSARS-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.Fang TianBei TongLiang SunShengchao ShiBin ZhengZibin WangXianchi DongPeng ZhengeLife Sciences Publications LtdarticleSARS-CoV-2 spike proteinsingle-molecule force spectroscopyMD simulationsprotein–protein interactionMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	SARS-CoV-2 spike protein single-molecule force spectroscopy MD simulations protein–protein interaction Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	SARS-CoV-2 spike protein single-molecule force spectroscopy MD simulations protein–protein interaction Medicine R Science Q Biology (General) QH301-705.5 Fang Tian Bei Tong Liang Sun Shengchao Shi Bin Zheng Zibin Wang Xianchi Dong Peng Zheng N501Y mutation of spike protein in SARS-CoV-2 strengthens its binding to receptor ACE2
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	article
author	Fang Tian Bei Tong Liang Sun Shengchao Shi Bin Zheng Zibin Wang Xianchi Dong Peng Zheng
author_facet	Fang Tian Bei Tong Liang Sun Shengchao Shi Bin Zheng Zibin Wang Xianchi Dong Peng Zheng
author_sort	Fang Tian
title	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_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_sort	n501y mutation of spike protein in sars-cov-2 strengthens its binding to receptor ace2
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/6d6d325ec0514285a12b3deb6ab193f0
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N501Y mutation of spike protein in SARS-CoV-2 strengthens its binding to receptor ACE2

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