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TitleCryo-EM structure of the SARS-CoV-2 3a ion channel in lipid nanodiscs.
Journal, issue, pagesbioRxiv, Year 2020
Publish dateJun 18, 2020
AuthorsDavid M Kern / Ben Sorum / Christopher M Hoel / Savitha Sridharan / Jonathan P Remis / Daniel B Toso / Stephen G Brohawn
PubMed AbstractSARS-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 ...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 forms large conductance cation channels and present cryo-EM structures of dimeric and tetrameric SARS-CoV-2 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 and that infect bats and humans, suggesting therapeutics targeting 3a could treat a range of coronaviral diseases.
External linksPubMed:32587976 / Publisher's page
KeywordsTRANSPORT PROTEIN / SARS-CoV-2 / coronavirus / viroporin / ion channel
MethodsEM (single particle)
Resolution2.9 - 6.5 A
Structure data

EMDB-22136:
Cryo-EM structure of SARS-CoV-2 ORF3a

EMDB-22138:
Tetrameric SARS-CoV-2 ORF3a in a lipid nanodisc

EMDB-22139:
SARS-CoV-2 ORF3a with Emodin in a MSP1E3D1 lipid nanodisc

PDB-6xdc:
Cryo-EM structure of SARS-CoV-2 ORF3a

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  • severe acute respiratory syndrome coronavirus 2

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