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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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    as
    1. Medini Manohar Ghodgaonkar & Patrick Kehl & Ilenia Ventura & Liyan Hu & Margherita Bignami & Josef Jiricny, 2014. "Phenotypic characterization of missense polymerase-δ mutations using an inducible protein-replacement system," Nature Communications, Nature, vol. 5(1), pages 1-8, December.
    2. M. Amaral & D. B. Kokh & J. Bomke & A. Wegener & H. P. Buchstaller & H. M. Eggenweiler & P. Matias & C. Sirrenberg & R. C. Wade & M. Frech, 2017. "Protein conformational flexibility modulates kinetics and thermodynamics of drug binding," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    3. Paulina Prorok & Marie Artufel & Antoine Aze & Philippe Coulombe & Isabelle Peiffer & Laurent Lacroix & Aurore Guédin & Jean-Louis Mergny & Julia Damaschke & Aloys Schepers & Christelle Cayrou & Marie, 2019. "Involvement of G-quadruplex regions in mammalian replication origin activity," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    4. Philip Zegerman & John F. X. Diffley, 2007. "Phosphorylation of Sld2 and Sld3 by cyclin-dependent kinases promotes DNA replication in budding yeast," Nature, Nature, vol. 445(7125), pages 281-285, January.
    5. Markus Sauer & Stefan A. Juranek & James Marks & Alessio Magis & Hinke G. Kazemier & Daniel Hilbig & Daniel Benhalevy & Xiantao Wang & Markus Hafner & Katrin Paeschke, 2019. "DHX36 prevents the accumulation of translationally inactive mRNAs with G4-structures in untranslated regions," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    6. Li-Wei Chang & Tyler K. Lytle & Mithun Radhakrishna & Jason J. Madinya & Jon Vélez & Charles E. Sing & Sarah L. Perry, 2017. "Sequence and entropy-based control of complex coacervates," Nature Communications, Nature, vol. 8(1), pages 1-8, December.
    7. Katrin Paeschke & Matthew L. Bochman & P. Daniela Garcia & Petr Cejka & Katherine L. Friedman & Stephen C. Kowalczykowski & Virginia A. Zakian, 2013. "Pif1 family helicases suppress genome instability at G-quadruplex motifs," Nature, Nature, vol. 497(7450), pages 458-462, May.
    8. Sebastian Kaiser & Florian Sauer & Caroline Kisker, 2017. "The structural and functional characterization of human RecQ4 reveals insights into its helicase mechanism," Nature Communications, Nature, vol. 8(1), pages 1-12, August.
    9. Seiji Tanaka & Toshiko Umemori & Kazuyuki Hirai & Sachiko Muramatsu & Yoichiro Kamimura & Hiroyuki Araki, 2007. "CDK-dependent phosphorylation of Sld2 and Sld3 initiates DNA replication in budding yeast," Nature, Nature, vol. 445(7125), pages 328-332, January.
    10. Thomas Evangelidis & Santrupti Nerli & Jiří Nováček & Andrew E. Brereton & P. Andrew Karplus & Rochelle R. Dotas & Vincenzo Venditti & Nikolaos G. Sgourakis & Konstantinos Tripsianes, 2018. "Automated NMR resonance assignments and structure determination using a minimal set of 4D spectra," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    11. Andrea Sottini & Alessandro Borgia & Madeleine B. Borgia & Katrine Bugge & Daniel Nettels & Aritra Chowdhury & Pétur O. Heidarsson & Franziska Zosel & Robert B. Best & Birthe B. Kragelund & Benjamin S, 2020. "Polyelectrolyte interactions enable rapid association and dissociation in high-affinity disordered protein complexes," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    12. Shiou-Ru Tzeng & Charalampos G. Kalodimos, 2009. "Dynamic activation of an allosteric regulatory protein," Nature, Nature, vol. 462(7271), pages 368-372, November.
    13. Alessandro Borgia & Madeleine B. Borgia & Katrine Bugge & Vera M. Kissling & Pétur O. Heidarsson & Catarina B. Fernandes & Andrea Sottini & Andrea Soranno & Karin J. Buholzer & Daniel Nettels & Birthe, 2018. "Extreme disorder in an ultrahigh-affinity protein complex," Nature, Nature, vol. 555(7694), pages 61-66, March.
    14. Jae-Yeol Kim & Fanjie Meng & Janghyun Yoo & Hoi Sung Chung, 2018. "Diffusion-limited association of disordered protein by non-native electrostatic interactions," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
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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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