Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Cryo-EM structure of the SARS-CoV-2 3a ion channel in lipid nanodiscs

View ORCID ProfileDavid M. Kern, View ORCID ProfileBen Sorum, View ORCID ProfileChristopher M. Hoel, Savitha Sridharan, Jonathan P. Remis, Daniel B. Toso, View ORCID ProfileStephen G. Brohawn
doi: https://doi.org/10.1101/2020.06.17.156554
David M. Kern
1Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, California, 94720, USA
2Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, California, 94720, USA
3California Institute for Quantitative Biology (QB3), University of California Berkeley, Berkeley, CA 94720, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for David M. Kern
Ben Sorum
1Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, California, 94720, USA
2Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, California, 94720, USA
3California Institute for Quantitative Biology (QB3), University of California Berkeley, Berkeley, CA 94720, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ben Sorum
Christopher M. Hoel
1Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, California, 94720, USA
2Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, California, 94720, USA
3California Institute for Quantitative Biology (QB3), University of California Berkeley, Berkeley, CA 94720, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Christopher M. Hoel
Savitha Sridharan
1Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, California, 94720, USA
2Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, California, 94720, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jonathan P. Remis
3California Institute for Quantitative Biology (QB3), University of California Berkeley, Berkeley, CA 94720, USA
4Molecular Biophysics and Integrative Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Daniel B. Toso
3California Institute for Quantitative Biology (QB3), University of California Berkeley, Berkeley, CA 94720, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stephen G. Brohawn
1Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, California, 94720, USA
2Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, California, 94720, USA
3California Institute for Quantitative Biology (QB3), University of California Berkeley, Berkeley, CA 94720, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Stephen G. Brohawn
  • For correspondence: brohawn@berkeley.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Data/Code
  • Preview PDF
Loading

Abstract

SARS-CoV-2 encodes three putative ion channels: E, 8a, and 3a. In related SARS-CoV-1, 3a is implicated in viral release, inflammasome activation, and cell death and its deletion reduces viral titer and morbidity in animal models, suggesting 3a-targeted therapeutics could treat SARS and COVID-19. However, the structural basis for the function of 3a is unknown. Here, we show that SARS-CoV-2 3a forms large conductance cation channels and present cryo-EM structures of dimeric and tetrameric 3a in lipid nanodiscs. 3a adopts a novel fold and is captured in a closed or inactivated state. A narrow bifurcated exterior pore precludes conduction and leads to a large polar cavity open to the cytosol. 3a function is conserved in a common variant among circulating SARS-CoV-2 that alters the channel pore. We identify 3a-like proteins in all Alpha- and Beta-coronaviruses that infect bats and humans, suggesting therapeutics targeting 3a could treat a range of coronaviral diseases.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://www.rcsb.org/structure/6XDC

  • https://www.emdataresource.org/EMD-22136

  • https://www.emdataresource.org/EMD-22138

  • https://www.emdataresource.org/EMD-22139

  • https://www.ebi.ac.uk/pdbe/emdb/empiar/entry/10439/

  • https://www.ebi.ac.uk/pdbe/emdb/empiar/entry/10440/

  • https://www.ebi.ac.uk/pdbe/emdb/empiar/entry/10441/

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
Back to top
PreviousNext
Posted June 25, 2020.
Download PDF
Data/Code
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Cryo-EM structure of the SARS-CoV-2 3a ion channel in lipid nanodiscs
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Cryo-EM structure of the SARS-CoV-2 3a ion channel in lipid nanodiscs
David M. Kern, Ben Sorum, Christopher M. Hoel, Savitha Sridharan, Jonathan P. Remis, Daniel B. Toso, Stephen G. Brohawn
bioRxiv 2020.06.17.156554; doi: https://doi.org/10.1101/2020.06.17.156554
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Cryo-EM structure of the SARS-CoV-2 3a ion channel in lipid nanodiscs
David M. Kern, Ben Sorum, Christopher M. Hoel, Savitha Sridharan, Jonathan P. Remis, Daniel B. Toso, Stephen G. Brohawn
bioRxiv 2020.06.17.156554; doi: https://doi.org/10.1101/2020.06.17.156554

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Biophysics
Subject Areas
All Articles
  • Animal Behavior and Cognition (3609)
  • Biochemistry (7585)
  • Bioengineering (5533)
  • Bioinformatics (20825)
  • Biophysics (10344)
  • Cancer Biology (7995)
  • Cell Biology (11653)
  • Clinical Trials (138)
  • Developmental Biology (6617)
  • Ecology (10224)
  • Epidemiology (2065)
  • Evolutionary Biology (13639)
  • Genetics (9557)
  • Genomics (12856)
  • Immunology (7930)
  • Microbiology (19568)
  • Molecular Biology (7675)
  • Neuroscience (42182)
  • Paleontology (308)
  • Pathology (1259)
  • Pharmacology and Toxicology (2208)
  • Physiology (3271)
  • Plant Biology (7058)
  • Scientific Communication and Education (1295)
  • Synthetic Biology (1953)
  • Systems Biology (5433)
  • Zoology (1119)