A 3.4-Å cryo-electron microscopy structure of the human coronavirus spike trimer computationally derived from vitrified NL63 virus particles
Abstract
Human coronavirus NL63 (HCoV-NL63) is an enveloped pathogen of the family Coronaviridae that spreads worldwide and causes up to 10% of all annual respiratory diseases. HCoV-NL63 is typically associated with mild upper respiratory symptoms in children, elderly and immunocompromised individuals. It has also been shown to cause severe lower respiratory illness. NL63 shares ACE2 as a receptor for viral entry with SARS-CoV-1 and SARS-CoV-2. Here we present the in situ structure of HCoV-NL63 spike (S) trimer at 3.4-Å resolution by single-particle cryo-EM imaging of vitrified virions without chemical fixative. It is structurally homologous to that obtained previously from the biochemically purified ectodomain of HCoV-NL63 S trimer, which displays a 3-fold symmetric trimer in a single conformation. In addition to previously proposed and observed glycosylation sites, our map shows density at other sites, as well as different glycan structures. The domain arrangement within a protomer is strikingly different from that of the SARS-CoV-2 S and may explain their different requirements for activating binding to the receptor. Overall, this structure provides the basis for future studies of spike proteins with receptors, antibodies, or drugs, in the native state of the coronavirus particles.
- Authors:
-
[1];
[1];
[1];
[1];
[2];
[3];
[3];
[4]
- Stanford Univ., CA (United States)
- SLAC National Accelerator Lab., Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL)
- Vitalant Research Inst., San Francisco, CA (United States)
- Stanford Univ., CA (United States); SLAC National Accelerator Lab., Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL)
- Publication Date:
- Research Org.:
- SLAC National Accelerator Lab., Menlo Park, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC); National Institutes of Health (NIH)
- OSTI Identifier:
- 1717875
- Grant/Contract Number:
- AC02-76SF00515; P41GM103832; R01AI148382; P01AI120943; R01GM079429; U24GM129564
- Resource Type:
- Accepted Manuscript
- Journal Name:
- QRB Discovery
- Additional Journal Information:
- Journal Volume: 1; Journal Issue: e11; Journal ID: ISSN 2633-2892
- Publisher:
- Cambridge University Press
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Human coronavirus NL63; spike trimer; cryo-EM
Citation Formats
Zhang, Kaiming, Li, Shanshan, Pintilie, Grigore, Chmielewski, David, Schmid, Michael F., Simmons, Graham, Jin, Jing, and Chiu, Wah. A 3.4-Å cryo-electron microscopy structure of the human coronavirus spike trimer computationally derived from vitrified NL63 virus particles. United States: N. p., 2020.
Web. doi:10.1017/qrd.2020.16.
Zhang, Kaiming, Li, Shanshan, Pintilie, Grigore, Chmielewski, David, Schmid, Michael F., Simmons, Graham, Jin, Jing, & Chiu, Wah. A 3.4-Å cryo-electron microscopy structure of the human coronavirus spike trimer computationally derived from vitrified NL63 virus particles. United States. https://doi.org/10.1017/qrd.2020.16
Zhang, Kaiming, Li, Shanshan, Pintilie, Grigore, Chmielewski, David, Schmid, Michael F., Simmons, Graham, Jin, Jing, and Chiu, Wah. Tue .
"A 3.4-Å cryo-electron microscopy structure of the human coronavirus spike trimer computationally derived from vitrified NL63 virus particles". United States. https://doi.org/10.1017/qrd.2020.16. https://www.osti.gov/servlets/purl/1717875.
@article{osti_1717875,
title = {A 3.4-Å cryo-electron microscopy structure of the human coronavirus spike trimer computationally derived from vitrified NL63 virus particles},
author = {Zhang, Kaiming and Li, Shanshan and Pintilie, Grigore and Chmielewski, David and Schmid, Michael F. and Simmons, Graham and Jin, Jing and Chiu, Wah},
abstractNote = {Human coronavirus NL63 (HCoV-NL63) is an enveloped pathogen of the family Coronaviridae that spreads worldwide and causes up to 10% of all annual respiratory diseases. HCoV-NL63 is typically associated with mild upper respiratory symptoms in children, elderly and immunocompromised individuals. It has also been shown to cause severe lower respiratory illness. NL63 shares ACE2 as a receptor for viral entry with SARS-CoV-1 and SARS-CoV-2. Here we present the in situ structure of HCoV-NL63 spike (S) trimer at 3.4-Å resolution by single-particle cryo-EM imaging of vitrified virions without chemical fixative. It is structurally homologous to that obtained previously from the biochemically purified ectodomain of HCoV-NL63 S trimer, which displays a 3-fold symmetric trimer in a single conformation. In addition to previously proposed and observed glycosylation sites, our map shows density at other sites, as well as different glycan structures. The domain arrangement within a protomer is strikingly different from that of the SARS-CoV-2 S and may explain their different requirements for activating binding to the receptor. Overall, this structure provides the basis for future studies of spike proteins with receptors, antibodies, or drugs, in the native state of the coronavirus particles.},
doi = {10.1017/qrd.2020.16},
journal = {QRB Discovery},
number = e11,
volume = 1,
place = {United States},
year = {Tue Nov 17 00:00:00 EST 2020},
month = {Tue Nov 17 00:00:00 EST 2020}
}
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