9I22

Structure of Human helicase RecQ1- Myc G-quadruplex - ADP complex

Summary for 9I22

• Entry DOI: 10.2210/pdb9i22/pdb
• Descriptor: ATP-dependent DNA helicase Q1, DNA (5'-D(P*GP*GP*GP*TP*GP*GP*GP*TP*AP*GP*GP*GP*TP*GP*GP*GP*T)-3'), ZINC ION, ... (7 entities in total)
• Functional Keywords: helicase dna g-quadruplex, hydrolase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 137479.87

Authors

Song, Z.Y.,Liu, N.N.,Ai, X.,Rety, S.,Xi, X.G. (deposition date: 2025-01-17, release date: 2025-10-01)

Primary citation

Song, Z.Y.,Zhang, X.,Ai, X.,Huang, L.Y.,Hou, X.M.,Fosse, P.,Liu, N.N.,Mauffret, O.,Rety, S.,Xi, X.G.
Structural mechanism of RECQ1 helicase in unfolding G-quadruplexes compared with duplex DNA.
Nucleic Acids Res., 53:-, 2025

PubMed Abstract: RECQ1, the most abundant RecQ helicase in human cells, is involved in telomere maintenance in ALT cells and plays a critical role in maintaining genomic integrity and stability. Here, we present five high-resolution crystal structures that systematically reveal a novel mechanism by which the RECQ1 helicase recognizes and regulates G-quadruplex (G4) DNA structures. Our results demonstrate that DNA binding induces intra-subunit rearrangement in RECQ1, transitioning it from a closed to an open conformation. This rearrangement alters the stability of the dimer interface. G4 recognition and unwinding are driven by coordinated interactions between the D1/D2 domains and the single-stranded DNA (ssDNA)-binding channel. This dual engagement aligns the G4 tetrad in a geometry favorable for unwinding. ATP hydrolysis facilitates ssDNA translocation, positioning the β-hairpin to disrupt hydrogen bonds-unraveling G4 structures in a manner analogous to the unwinding of dsDNA. This study proposes a mechanistic model for RECQ1-mediated G4 unwinding and elucidates how RECQ1 recognizes and unwinds distinct DNA structures.

PubMed: 40966504
DOI: 10.1093/nar/gkaf877

Experimental method

X-RAY DIFFRACTION (2.42 Å)