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SARS-CoV-2 nsp3-4 suffice to form a pore shaping replication organelles
Liv Zimmermann; Xiaohan Zhao; Jana Makroczyova; Moritz Wachsmuth-Melm; Vibhu Prasad; Ralf Bartenschlager; Petr Chlanda.
Affiliation
  • Liv Zimmermann; Department of Infectious Diseases, Virology, Heidelberg University Hospital, Heidelberg, Germany
  • Xiaohan Zhao; Department of Infectious Diseases, Virology, Heidelberg University Hospital, Heidelberg, Germany
  • Jana Makroczyova; Department of Infectious Diseases, Virology, Heidelberg University Hospital, Heidelberg, Germany
  • Moritz Wachsmuth-Melm; Department of Infectious Diseases, Virology, Heidelberg University Hospital, Heidelberg, Germany
  • Vibhu Prasad; Department of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany
  • Ralf Bartenschlager; Department of Infectious Diseases, Virology, Heidelberg University, Heidelberg, Germany
  • Petr Chlanda; Department of Infectious Diseases, Virology, Heidelberg University Hospital, Heidelberg, Germany
Preprint de En | PREPRINT-BIORXIV | ID: ppbiorxiv-513196
ABSTRACT
Coronavirus replication is associated with the remodeling of cellular membranes resulting in the formation of double-membrane vesicles (DMVs). Recently, a pore spanning DMV was identified as a putative portal for viral RNA transcription and replication products providing a novel target for antiviral intervention. However, the exact components and the structure of the SARS-CoV-2 pore remain to be determined. Here, we investigate the structure of DMV pores by in situ cryo-electron tomography combined with subtomogram averaging. We reveal non-structural proteins (nsp) 3 and 4 as minimal components forming a DMV spanning pore and show that nsp3 Ubl1-Ubl2 domains are critical for inducing membrane curvature and DMV formation. Altogether, SARS-CoV-2 nsp3-4 has a dual role by driving the biogenesis of replication organelles and forming DMV-spanning replicopores. One-Sentence SummaryBiogenesis of SARS-CoV-2 replication organelles is driven by nsp3-4 constituting the double-membrane vesicle spanning pore.
Licence
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Texte intégral: 1 Collection: 09-preprints Base de données: PREPRINT-BIORXIV Langue: En Année: 2022 Type de document: Preprint
Texte intégral: 1 Collection: 09-preprints Base de données: PREPRINT-BIORXIV Langue: En Année: 2022 Type de document: Preprint