Cryo-electron microscopy structures of the N501Y SARS-CoV-2 spike protein in complex with ACE2 and 2 potent neutralizing antibodies.

The recently reported "UK variant" (B.1.1.7) of SARS-CoV-2 is thought to be more infectious than previously circulating strains as a result of several changes, including the N501Y mutation. We present a 2.9-Å resolution cryo-electron microscopy (cryo-EM) structure of the complex between th...

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Autores principales:	Xing Zhu, Dhiraj Mannar, Shanti S Srivastava, Alison M Berezuk, Jean-Philippe Demers, James W Saville, Karoline Leopold, Wei Li, Dimiter S Dimitrov, Katharine S Tuttle, Steven Zhou, Sagar Chittori, Sriram Subramaniam
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/3c1f36e42d5749cfa2e5fb28488e1f6f
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spelling	oai:doaj.org-article:3c1f36e42d5749cfa2e5fb28488e1f6f2021-12-02T19:54:43ZCryo-electron microscopy structures of the N501Y SARS-CoV-2 spike protein in complex with ACE2 and 2 potent neutralizing antibodies.1544-91731545-788510.1371/journal.pbio.3001237https://doaj.org/article/3c1f36e42d5749cfa2e5fb28488e1f6f2021-04-01T00:00:00Zhttps://doi.org/10.1371/journal.pbio.3001237https://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885The recently reported "UK variant" (B.1.1.7) of SARS-CoV-2 is thought to be more infectious than previously circulating strains as a result of several changes, including the N501Y mutation. We present a 2.9-Å resolution cryo-electron microscopy (cryo-EM) structure of the complex between the ACE2 receptor and N501Y spike protein ectodomains that shows Y501 inserted into a cavity at the binding interface near Y41 of ACE2. This additional interaction provides a structural explanation for the increased ACE2 affinity of the N501Y mutant, and likely contributes to its increased infectivity. However, this mutation does not result in large structural changes, enabling important neutralization epitopes to be retained in the spike receptor binding domain. We confirmed this through biophysical assays and by determining cryo-EM structures of spike protein ectodomains bound to 2 representative potent neutralizing antibody fragments.Xing ZhuDhiraj MannarShanti S SrivastavaAlison M BerezukJean-Philippe DemersJames W SavilleKaroline LeopoldWei LiDimiter S DimitrovKatharine S TuttleSteven ZhouSagar ChittoriSriram SubramaniamPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 19, Iss 4, p e3001237 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Xing Zhu Dhiraj Mannar Shanti S Srivastava Alison M Berezuk Jean-Philippe Demers James W Saville Karoline Leopold Wei Li Dimiter S Dimitrov Katharine S Tuttle Steven Zhou Sagar Chittori Sriram Subramaniam Cryo-electron microscopy structures of the N501Y SARS-CoV-2 spike protein in complex with ACE2 and 2 potent neutralizing antibodies.
description	The recently reported "UK variant" (B.1.1.7) of SARS-CoV-2 is thought to be more infectious than previously circulating strains as a result of several changes, including the N501Y mutation. We present a 2.9-Å resolution cryo-electron microscopy (cryo-EM) structure of the complex between the ACE2 receptor and N501Y spike protein ectodomains that shows Y501 inserted into a cavity at the binding interface near Y41 of ACE2. This additional interaction provides a structural explanation for the increased ACE2 affinity of the N501Y mutant, and likely contributes to its increased infectivity. However, this mutation does not result in large structural changes, enabling important neutralization epitopes to be retained in the spike receptor binding domain. We confirmed this through biophysical assays and by determining cryo-EM structures of spike protein ectodomains bound to 2 representative potent neutralizing antibody fragments.
format	article
author	Xing Zhu Dhiraj Mannar Shanti S Srivastava Alison M Berezuk Jean-Philippe Demers James W Saville Karoline Leopold Wei Li Dimiter S Dimitrov Katharine S Tuttle Steven Zhou Sagar Chittori Sriram Subramaniam
author_facet	Xing Zhu Dhiraj Mannar Shanti S Srivastava Alison M Berezuk Jean-Philippe Demers James W Saville Karoline Leopold Wei Li Dimiter S Dimitrov Katharine S Tuttle Steven Zhou Sagar Chittori Sriram Subramaniam
author_sort	Xing Zhu
title	Cryo-electron microscopy structures of the N501Y SARS-CoV-2 spike protein in complex with ACE2 and 2 potent neutralizing antibodies.
title_short	Cryo-electron microscopy structures of the N501Y SARS-CoV-2 spike protein in complex with ACE2 and 2 potent neutralizing antibodies.
title_full	Cryo-electron microscopy structures of the N501Y SARS-CoV-2 spike protein in complex with ACE2 and 2 potent neutralizing antibodies.
title_fullStr	Cryo-electron microscopy structures of the N501Y SARS-CoV-2 spike protein in complex with ACE2 and 2 potent neutralizing antibodies.
title_full_unstemmed	Cryo-electron microscopy structures of the N501Y SARS-CoV-2 spike protein in complex with ACE2 and 2 potent neutralizing antibodies.
title_sort	cryo-electron microscopy structures of the n501y sars-cov-2 spike protein in complex with ace2 and 2 potent neutralizing antibodies.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/3c1f36e42d5749cfa2e5fb28488e1f6f
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Cryo-electron microscopy structures of the N501Y SARS-CoV-2 spike protein in complex with ACE2 and 2 potent neutralizing antibodies.

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