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Structural mechanism underpinning Thermus oshimai Pif1-mediated G-quadruplex unfolding.
EMBO Rep:e53874.
G-quadruplexes (G4s) are unusual stable DNA structures that cause genomicinstability. To overcome the potential barriers formed by G4s, cells have evolveddifferent families of proteins that unfold G4s. Pif1 is a DNA helicase fromsuperfamily 1 (SF1) conserved from bacteria to humans with high G4-unwindingactivity. Here, we present the first X-ray crystal structure of the Thermusoshimai Pif1 (ToPif1) complexed with a G4. Our structure reveals that ToPif1recognizes the entire native G4 via a cluster of amino acids at domains 1B/2Bwhich constitute a G4-Recognizing Surface (GRS). The overall structure of the G4maintains its three-layered propeller-type G4 topology, without significantreorganization of G-tetrads upon protein binding. The three G-tetrads in G4 arerecognized by GRS residues mainly through electrostatic, ionic interactions, andhydrogen bonds formed between the GRS residues and the ribose-phosphate backbone.Compared with previously solved structures of SF2 helicases in complex with G4,our structure reveals how helicases from distinct superfamilies adopt differentstrategies for recognizing and unfolding G4s.
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