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

Author:

Wolff Georg1ORCID,Limpens Ronald W. A. L.1ORCID,Zevenhoven-Dobbe Jessika C.2,Laugks Ulrike3ORCID,Zheng Shawn4ORCID,de Jong Anja W. M.1ORCID,Koning Roman I.1ORCID,Agard David A.5ORCID,Grünewald Kay36ORCID,Koster Abraham J.1ORCID,Snijder Eric J.2ORCID,Bárcena Montserrat1ORCID

Affiliation:

1. Section Electron Microscopy, Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden 2333 ZC, Netherlands.

2. Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden 2333 ZA, Netherlands.

3. Department of Structural Cell Biology of Viruses, Centre for Structural Systems Biology, Heinrich Pette Institute, Leibnitz Institute of Experimental Virology, 22607 Hamburg, Germany.

4. Howard Hughes Medical Institute, Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94143, USA.

5. Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94143, USA.

6. Department of Chemistry, MIN Faculty, Universität Hamburg, 20146 Hamburg, Germany.

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.

Funder

National Institutes of Health

H2020 Health

Deutsche Forschungsgemeinschaft

Nederlandse Organisatie voor Wetenschappelijk Onderzoek

Bundesministerium für Bildung und Forschung

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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