Summary information and primary citation

PDB-id
9i23
Class
hydrolase
Method
X-ray (3.69 Å)
Summary
Structure of human helicase recq1- 795-2t g-quadruplex - adp complex
Reference
Song ZY, Zhang X, Ai X, Huang LY, Hou XM, Fosse P, Liu NN, Mauffret O, Rety S, Xi XG (2025): "Structural mechanism of RECQ1 helicase in unfolding G-quadruplexes compared with duplex DNA." Nucleic Acids Res., 53. doi: 10.1093/nar/gkaf877.
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.
G4 notes
3 G-tetrads, 1 G4 helix, 1 G4 stem, UUUU, parallel, 4+0, 3(-P-P-P)

Cartoon-block schematics in six views (download the tarball)

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List of 3 G-tetrads

 1 glyco-bond=---- sugar=---- groove=---- planarity=0.095 type=planar O+ nts=4 GGGG 1:C.DG2,1:C.DG6,1:C.DG10,1:C.DG14
 2 glyco-bond=---- sugar=---- groove=---- planarity=0.108 type=planar O+ nts=4 GGGG 1:C.DG3,1:C.DG7,1:C.DG11,1:C.DG15
 3 glyco-bond=---- sugar=.--- groove=---- planarity=0.126 type=planar O+ nts=4 GGGG 1:C.DG4,1:C.DG8,1:C.DG12,1:C.DG16

List of 1 G4-helix

In DSSR, a G4-helix is defined by stacking interactions of G-tetrads, regardless of backbone connectivity, and may contain more than one G4-stem.

Helix#1, 3 G-tetrads, INTRA-molecular, with 1 stem
 1  glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG 1:C.DG2,1:C.DG6,1:C.DG10,1:C.DG14
 2  glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG 1:C.DG3,1:C.DG7,1:C.DG11,1:C.DG15
 3  glyco-bond=---- sugar=.--- groove=---- WC-->Major O+ nts=4 GGGG 1:C.DG4,1:C.DG8,1:C.DG12,1:C.DG16
  step#1  pm(>>,forward)  area=12.33 rise=3.26 twist=32.8
  step#2  pm(>>,forward)  area=16.85 rise=3.34 twist=25.4
  strand#1 DNA glyco-bond=--- sugar=--. nts=3 GGG 1:C.DG2,1:C.DG3,1:C.DG4
  strand#2 DNA glyco-bond=--- sugar=--- nts=3 GGG 1:C.DG6,1:C.DG7,1:C.DG8
  strand#3 DNA glyco-bond=--- sugar=--- nts=3 GGG 1:C.DG10,1:C.DG11,1:C.DG12
  strand#4 DNA glyco-bond=--- sugar=--- nts=3 GGG 1:C.DG14,1:C.DG15,1:C.DG16

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2 stacking diagrams 
 1  glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG 1:C.DG2,1:C.DG6,1:C.DG10,1:C.DG14
 2  glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG 1:C.DG3,1:C.DG7,1:C.DG11,1:C.DG15
  step#1  pm(>>,forward)  area=12.33 rise=3.26 twist=32.8

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 2  glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG 1:C.DG3,1:C.DG7,1:C.DG11,1:C.DG15
 3  glyco-bond=---- sugar=.--- groove=---- WC-->Major O+ nts=4 GGGG 1:C.DG4,1:C.DG8,1:C.DG12,1:C.DG16
  step#2  pm(>>,forward)  area=16.85 rise=3.34 twist=25.4

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List of 1 G4-stem

In DSSR, a G4-stem is defined as a G4-helix with backbone connectivity. Bulges are also allowed along each of the four strands.

Stem#1, 3 G-tetrads, 3 loops, INTRA-molecular, UUUU, parallel, 4+0, 3(-P-P-P)
 1  glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG 1:C.DG2,1:C.DG6,1:C.DG10,1:C.DG14
 2  glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG 1:C.DG3,1:C.DG7,1:C.DG11,1:C.DG15
 3  glyco-bond=---- sugar=.--- groove=---- WC-->Major O+ nts=4 GGGG 1:C.DG4,1:C.DG8,1:C.DG12,1:C.DG16
  step#1  pm(>>,forward)  area=12.33 rise=3.26 twist=32.8
  step#2  pm(>>,forward)  area=16.85 rise=3.34 twist=25.4
  strand#1  U DNA glyco-bond=--- sugar=--. nts=3 GGG 1:C.DG2,1:C.DG3,1:C.DG4
  strand#2  U DNA glyco-bond=--- sugar=--- nts=3 GGG 1:C.DG6,1:C.DG7,1:C.DG8
  strand#3  U DNA glyco-bond=--- sugar=--- nts=3 GGG 1:C.DG10,1:C.DG11,1:C.DG12
  strand#4  U DNA glyco-bond=--- sugar=--- nts=3 GGG 1:C.DG14,1:C.DG15,1:C.DG16
  loop#1 type=propeller strands=[#1,#2] nts=1 T 1:C.DT5
  loop#2 type=propeller strands=[#2,#3] nts=1 T 1:C.DT9
  loop#3 type=propeller strands=[#3,#4] nts=1 T 1:C.DT13

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