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Concerted transformation of a hyper-paused transcription complex and its reinforcing protein

Author

Listed:
  • Philipp K. Zuber

    (Universität Bayreuth
    Cambridge Biomedical Campus)

  • Nelly Said

    (Freie Universität Berlin)

  • Tarek Hilal

    (Freie Universität Berlin
    Freie Universität Berlin)

  • Bing Wang

    (The Ohio State University)

  • Bernhard Loll

    (Freie Universität Berlin)

  • Jorge González-Higueras

    (Pontificia Universidad Católica de Chile
    Millennium Institute for Integrative Biology)

  • César A. Ramírez-Sarmiento

    (Pontificia Universidad Católica de Chile
    Millennium Institute for Integrative Biology)

  • Georgiy A. Belogurov

    (University of Turku)

  • Irina Artsimovitch

    (The Ohio State University)

  • Markus C. Wahl

    (Freie Universität Berlin
    Helmholtz-Zentrum Berlin für Materialien und Energie)

  • Stefan H. Knauer

    (Universität Bayreuth
    Bristol-Myers Squibb GmbH & Co. KGaA)

Abstract

RfaH, a paralog of the universally conserved NusG, binds to RNA polymerases (RNAP) and ribosomes to activate expression of virulence genes. In free, autoinhibited RfaH, an α-helical KOW domain sequesters the RNAP-binding site. Upon recruitment to RNAP paused at an ops site, KOW is released and refolds into a β-barrel, which binds the ribosome. Here, we report structures of ops-paused transcription elongation complexes alone and bound to the autoinhibited and activated RfaH, which reveal swiveled, pre-translocated pause states stabilized by an ops hairpin in the non-template DNA. Autoinhibited RfaH binds and twists the ops hairpin, expanding the RNA:DNA hybrid to 11 base pairs and triggering the KOW release. Once activated, RfaH hyper-stabilizes the pause, which thus requires anti-backtracking factors for escape. Our results suggest that the entire RfaH cycle is solely determined by the ops and RfaH sequences and provide insights into mechanisms of recruitment and metamorphosis of NusG homologs across all life.

Suggested Citation

  • Philipp K. Zuber & Nelly Said & Tarek Hilal & Bing Wang & Bernhard Loll & Jorge González-Higueras & César A. Ramírez-Sarmiento & Georgiy A. Belogurov & Irina Artsimovitch & Markus C. Wahl & Stefan H., 2024. "Concerted transformation of a hyper-paused transcription complex and its reinforcing protein," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47368-4
    DOI: 10.1038/s41467-024-47368-4
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    References listed on IDEAS

    as
    1. Philipp Konrad Zuber & Kristian Schweimer & Paul Rösch & Irina Artsimovitch & Stefan H. Knauer, 2019. "Reversible fold-switching controls the functional cycle of the antitermination factor RfaH," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    2. Lauren L. Porter & Allen K. Kim & Swechha Rimal & Loren L. Looger & Ananya Majumdar & Brett D. Mensh & Mary R. Starich & Marie-Paule Strub, 2022. "Many dissimilar NusG protein domains switch between α-helix and β-sheet folds," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Ario Marco & Nick Berrow & Mario Lebendiker & Maria Garcia-Alai & Stefan H. Knauer & Blanca Lopez-Mendez & André Matagne & Annabel Parret & Kim Remans & Stephan Uebel & Bertrand Raynal, 2021. "Quality control of protein reagents for the improvement of research data reproducibility," Nature Communications, Nature, vol. 12(1), pages 1-4, December.
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