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Structure of influenza A polymerase bound to the viral RNA promoter

Author

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  • Alexander Pflug

    (European Molecular Biology Laboratory, Grenoble Outstation, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France
    University Grenoble Alpes-Centre National de la Recherche Scientifique-EMBL Unit of Virus Host-Cell Interactions, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France)

  • Delphine Guilligay

    (European Molecular Biology Laboratory, Grenoble Outstation, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France
    University Grenoble Alpes-Centre National de la Recherche Scientifique-EMBL Unit of Virus Host-Cell Interactions, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France)

  • Stefan Reich

    (European Molecular Biology Laboratory, Grenoble Outstation, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France
    University Grenoble Alpes-Centre National de la Recherche Scientifique-EMBL Unit of Virus Host-Cell Interactions, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France)

  • Stephen Cusack

    (European Molecular Biology Laboratory, Grenoble Outstation, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France
    University Grenoble Alpes-Centre National de la Recherche Scientifique-EMBL Unit of Virus Host-Cell Interactions, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France)

Abstract

The influenza virus polymerase transcribes or replicates the segmented RNA genome (viral RNA) into viral messenger RNA or full-length copies. To initiate RNA synthesis, the polymerase binds to the conserved 3′ and 5′ extremities of the viral RNA. Here we present the crystal structure of the heterotrimeric bat influenza A polymerase, comprising subunits PA, PB1 and PB2, bound to its viral RNA promoter. PB1 contains a canonical RNA polymerase fold that is stabilized by large interfaces with PA and PB2. The PA endonuclease and the PB2 cap-binding domain, involved in transcription by cap-snatching, form protrusions facing each other across a solvent channel. The 5′ extremity of the promoter folds into a compact hook that is bound in a pocket formed by PB1 and PA close to the polymerase active site. This structure lays the basis for an atomic-level mechanistic understanding of the many functions of influenza polymerase, and opens new opportunities for anti-influenza drug design.

Suggested Citation

  • Alexander Pflug & Delphine Guilligay & Stefan Reich & Stephen Cusack, 2014. "Structure of influenza A polymerase bound to the viral RNA promoter," Nature, Nature, vol. 516(7531), pages 355-360, December.
    • Handle: RePEc:nat:nature:v:516:y:2014:i:7531:d:10.1038_nature14008
    DOI: 10.1038/nature14008
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    Cited by:

    1. Franziska Günl & Tim Krischuns & Julian A. Schreiber & Lea Henschel & Marius Wahrenburg & Hannes C. A. Drexler & Sebastian A. Leidel & Vlad Cojocaru & Guiscard Seebohm & Alexander Mellmann & Martin Sc, 2023. "The ubiquitination landscape of the influenza A virus polymerase," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Jun Ma & Shuangyue Zhang & Xinzheng Zhang, 2021. "Structure of Machupo virus polymerase in complex with matrix protein Z," Nature Communications, Nature, vol. 12(1), pages 1-8, December.
    3. Tomas Kouba & Dominik Vogel & Sigurdur R. Thorkelsson & Emmanuelle R. J. Quemin & Harry M. Williams & Morlin Milewski & Carola Busch & Stephan Günther & Kay Grünewald & Maria Rosenthal & Stephen Cusac, 2021. "Conformational changes in Lassa virus L protein associated with promoter binding and RNA synthesis activity," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    4. Benoît Arragain & Quentin Durieux Trouilleton & Florence Baudin & Jan Provaznik & Nayara Azevedo & Stephen Cusack & Guy Schoehn & Hélène Malet, 2022. "Structural snapshots of La Crosse virus polymerase reveal the mechanisms underlying Peribunyaviridae replication and transcription," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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