A molecular pore spans the double membrane of the coronavirus replication organelle

Georg Wolff(Leiden University Medical Center), Ronald W.A.L. Limpens(Leiden University Medical Center), Jessika C. Zevenhoven-Dobbe(Leiden University Medical Center), Ulrike Laugks(Leibniz Institute of Virology (LIV)), Shawn Zheng(Howard Hughes Medical Institute), Anja W. M. de Jong(Leiden University Medical Center), Roman I. Koning(Leiden University Medical Center), David A. Agard(University of California, San Francisco), Kay Grünewald(Leibniz Institute of Virology (LIV)), Abraham J. Koster(Leiden University Medical Center), Eric J. Snijder(Leiden University Medical Center), Montserrat Bárcena(Leiden University Medical Center)
Science
August 6, 2020
Cited by 546Open Access
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Abstract

Coronavirus genome replication is associated with virus-induced cytosolic double-membrane vesicles, which may provide a tailored microenvironment for viral RNA synthesis in the infected cell. However, it is unclear how newly synthesized genomes and messenger RNAs can travel from these sealed replication compartments to the cytosol to ensure their translation and the assembly of progeny virions. In this study, we used cellular cryo-electron microscopy to visualize a molecular pore complex that spans both membranes of the double-membrane vesicle and would allow export of RNA to the cytosol. A hexameric assembly of a large viral transmembrane protein was found to form the core of the crown-shaped complex. This coronavirus-specific structure likely plays a key role in coronavirus replication and thus constitutes a potential drug target.


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