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Recognition and coacervation of G-quadruplexes by a multifunctional disordered region in RECQ4 helicase

Author

Listed:
  • Anna C. Papageorgiou

    (Masaryk University)

  • Michaela Pospisilova

    (Masaryk University
    Masaryk University)

  • Jakub Cibulka

    (Masaryk University)

  • Raghib Ashraf

    (Masaryk University)

  • Christopher A. Waudby

    (University College London
    University College London)

  • Pavel Kadeřávek

    (Masaryk University)

  • Volha Maroz

    (Masaryk University
    Masaryk University)

  • Karel Kubicek

    (Masaryk University
    Masaryk University
    Masaryk University)

  • Zbynek Prokop

    (Masaryk University
    St Anne’s University Hospital)

  • Lumir Krejci

    (Masaryk University
    Masaryk University
    St Anne’s University Hospital)

  • Konstantinos Tripsianes

    (Masaryk University)

Abstract

Biomolecular polyelectrolyte complexes can be formed between oppositely charged intrinsically disordered regions (IDRs) of proteins or between IDRs and nucleic acids. Highly charged IDRs are abundant in the nucleus, yet few have been functionally characterized. Here, we show that a positively charged IDR within the human ATP-dependent DNA helicase Q4 (RECQ4) forms coacervates with G-quadruplexes (G4s). We describe a three-step model of charge-driven coacervation by integrating equilibrium and kinetic binding data in a global numerical model. The oppositely charged IDR and G4 molecules form a complex in the solution that follows a rapid nucleation-growth mechanism leading to a dynamic equilibrium between dilute and condensed phases. We also discover a physical interaction with Replication Protein A (RPA) and demonstrate that the IDR can switch between the two extremes of the structural continuum of complexes. The structural, kinetic, and thermodynamic profile of its interactions revealed a dynamic disordered complex with nucleic acids and a static ordered complex with RPA protein. The two mutually exclusive binding modes suggest a regulatory role for the IDR in RECQ4 function by enabling molecular handoffs. Our study extends the functional repertoire of IDRs and demonstrates a role of polyelectrolyte complexes involved in G4 binding.

Suggested Citation

  • Anna C. Papageorgiou & Michaela Pospisilova & Jakub Cibulka & Raghib Ashraf & Christopher A. Waudby & Pavel Kadeřávek & Volha Maroz & Karel Kubicek & Zbynek Prokop & Lumir Krejci & Konstantinos Tripsi, 2023. "Recognition and coacervation of G-quadruplexes by a multifunctional disordered region in RECQ4 helicase," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42503-z
    DOI: 10.1038/s41467-023-42503-z
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    1. Johanna Luige & Alexandros Armaos & Gian Gaetano Tartaglia & Ulf Andersson Vang Ørom, 2024. "Predicting nuclear G-quadruplex RNA-binding proteins with roles in transcription and phase separation," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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