N501Y mutation of spike protein in SARS-CoV-2 strengthens its binding to receptor ACE2
- Nanjing University, China
- Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, China
Abstract
SARS-CoV-2 is 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), sharing a key mutation N501Y on the RBD, appear to be more infectious to humans. To understand the underlying mechanism, we performed cell surface binding assay, kinetics study, single-molecule technique, and 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 slower dissociation rate. Consistently, atomic force microscopy-based single-molecule force microscopy quantifies their strength showing a higher binding probability and unbinding force for the mutation. Molecular dynamics simulations of RBD-ACE2 complexes indicated that the N501Y introduced additional π-π and π-cation interaction for the higher force/interaction. Taken together, we suggested that the reinforced interaction from N501Y mutation in RBD should play an essential role in the higher transmission of SARS-CoV-2 variants and future mutations in the RBD of the virus should be under surveillance.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have provided for Figures 1-4.
Article and author information
Author details
Funding
National Key Research and Development Program of China (2020YFA0509000)
- Xianchi Dong
Fundamental Research Funds for the Central Universities (14380205)
- Peng Zheng
Natural Science Foundation of Jiangsu Province (BK20200058)
- Peng Zheng
Natural Science Foundation of Jiangsu Province (BK20202004)
- Peng Zheng
Natural Science Foundation of Jiangsu Province (BK20190275)
- Xianchi Dong
National Natural Science Foundation of China (21771103)
- Peng Zheng
National Natural Science Foundation of China (21977047)
- Peng Zheng
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Aaron Frank, University of Michigan, United States
Version history
- Preprint posted: February 15, 2021 (view preprint)
- Received: April 4, 2021
- Accepted: August 19, 2021
- Accepted Manuscript published: August 20, 2021 (version 1)
- Version of Record published: September 17, 2021 (version 2)
- Version of Record updated: December 14, 2021 (version 3)
Copyright
© 2021, Tian et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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N501Y mutation of spike protein in SARS-CoV-2 strengthens its binding to receptor ACE2
eLife 10:e69091.
https://doi.org/10.7554/eLife.69091
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