Glycan shield and epitope masking of a coronavirus spike protein observed by cryo-electron microscopy

Alexandra Walls 1 M Alejandra Tortorici 2 Brandon Frenz 1 Joost Snijder 1 Wentao Li 3 Félix A Rey 2 Frank Dimaio 1 Berend-Jan Bosch 3, * David Veesler 1, *
* Auteur correspondant
1 Department of Biochemistry [Washington ]
2 Virologie Structurale
3 Utrecht University [Utrecht]
Abstract : The threat of a major coronavirus pandemic urges the development of strategies to combat these pathogens. Human coronavirus NL63 (HCoV-NL63) is an α-coronavirus that can cause severe lower-respiratory-tract infections requiring hospitalization. We report here the 3.4-Å-resolution cryo-EM reconstruction of the HCoV-NL63 coronavirus spike glycoprotein trimer, which mediates entry into host cells and is the main target of neutralizing antibodies during infection. The map resolves the extensive glycan shield obstructing the protein surface and, in combination with mass spectrometry, provides a structural framework to understand the accessibility to antibodies. The structure reveals the complete architecture of the fusion machinery including the triggering loop and the C-terminal domains, which contribute to anchoring the trimer to the viral membrane. Our data further suggest that HCoV-NL63 and other coronaviruses use molecular trickery, based on epitope masking with glycans and activating conformational changes, to evade the immune system of infected hosts.
Keywords : Cryoelectron microscopy Glycoproteins Immunology Viral membrane fusion
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Article dans une revue
Nature Structural and Molecular Biology, Nature Publishing Group, 2016, 23 (10), pp.899 - 905. 〈10.1038/nsmb.3293〉
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Contributeur : M. Alejandra Tortorici <>
Soumis le : jeudi 14 décembre 2017 - 17:26:18
Dernière modification le : mercredi 21 novembre 2018 - 17:36:01

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Alexandra Walls, M Alejandra Tortorici, Brandon Frenz, Joost Snijder, Wentao Li, et al.. Glycan shield and epitope masking of a coronavirus spike protein observed by cryo-electron microscopy. Nature Structural and Molecular Biology, Nature Publishing Group, 2016, 23 (10), pp.899 - 905. 〈10.1038/nsmb.3293〉. 〈pasteur-01664348〉

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