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

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Publikace nespadá pod Lékařskou fakultu, ale pod Středoevropský technologický institut. Oficiální stránka publikace je na webu muni.cz.
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PAPAGEORGIOU Anna POSPÍŠILOVÁ Michaela CIBULKA Jakub ASHRAF Raghib WAUDBY Christopher KADEŘÁVEK Pavel MAROZ Volha KUBÍČEK Karel PROKOP Zbyněk KREJČÍ Lumír TRIPSIANES Konstantinos

Rok publikování 2023
Druh Článek v odborném periodiku
Časopis / Zdroj Nature Communications
Fakulta / Pracoviště MU

Středoevropský technologický institut

Citace
www https://www.nature.com/articles/s41467-023-42503-z
Doi http://dx.doi.org/10.1038/s41467-023-42503-z
Klíčová slova Biomolecular polyelectrolyte complexes; DNA helicase Q4; G-quadruplexes; intrinsically disordered regions; RPA protein
Přiložené soubory
Popis 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.
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