4.8 Article

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

Journal

SCIENCE
Volume 369, Issue 6509, Pages 1395-+

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abd3629

Keywords

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Funding

  1. Dutch Roadmap Grant NEMI (NWO grant) [184.034.014]
  2. NIH [R35GM118099, U19 AI135990]
  3. Howard Hughes Medical Institute
  4. BMBF [05K18BHA]
  5. DFG [EXC 2155, INST 152/772-1, INST 777-1 FUGG]
  6. wakeuptocorona crowdfunding initiative of the Leiden University Fund (LUF)
  7. LUMC Bontius Foundation
  8. SCORE project (European Union's Horizon 2020 research and innovation program) [101003627]

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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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