DSSR-enabled G4 identification/annotation: PDB entry 9uk8
Summary information and primary citation
- PDB-id
- 9uk8
- Class
- DNA
- Method
- X-ray (2.7 Å)
- Summary
- Monomeric antiparallel g-quadruplex formed by d(g4c2)4
- Reference
- Geng Y, Liu C, Miao H, Suen MC, Xie Y, Zhang B, Han W, Wu C, Ren H, Chen X, Tai HC, Wang Z, Zhu G, Cai Q (2025): "Crystal structures of distinct parallel and antiparallel DNA G-quadruplexes reveal structural polymorphism in C9orf72 G4C2 repeats." Nucleic Acids Res., 53. doi: 10.1093/nar/gkaf879.
- Abstract
- The abnormal expansion of GGGGCC (G4C2) repeats in the noncoding region of the C9orf72 gene is a major genetic cause of two devastating neurodegenerative disorders, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). These G4C2 repeats are known to form G-quadruplex (G4) structures, which are hypothesized to contribute to disease pathogenesis. Here, we demonstrated that four DNA G4C2 repeats can fold into two structurally distinct G4 conformations: a parallel and an antiparallel topology. The high-resolution crystal structure of the parallel G4 reveals an eight-layered dimeric assembly, formed by two identical monomeric units. Each unit contains four stacked G-tetrads connected by three propeller CC loops and is stabilized through 5'-to-5' π-π interactions and coordination with a central K+ ion. Notably, the 3'-ending cytosines form a C·C+·C·C+ quadruple base pair stacking onto the adjacent G-tetrad layer. In contrast, the antiparallel G4 adopts a four-layered monomeric structure with three edgewise loops, where the C6 and C18 bases engage in stacking interaction with neighboring G-tetrad via a K+ ion. These structurally distinct G-quadruplexes provide mechanistic insights into C9orf72-associated neurodegeneration and offer potential targets for the development of structure-based therapeutic strategies for ALS and FTD.
- G4 notes
- 4 G-tetrads, 1 G4 helix, 1 G4 stem, UDUD, anti-parallel:chair, 2+2, 4(+Ln+Lw+Ln)
Cartoon-block schematics in six views (download the tarball)
List of 4 G-tetrads
1 glyco-bond=s-s- sugar=---- groove=wnwn planarity=0.356 type=bowl O+ nts=4 GGGG 1:A.DG1,1:A.DG22,1:A.DG13,1:A.DG10 2 glyco-bond=-s-s sugar=-.-- groove=wnwn planarity=0.287 type=other O- nts=4 GGGG 1:A.DG2,1:A.DG21,1:A.DG14,1:A.DG9 3 glyco-bond=s-s- sugar=---- groove=wnwn planarity=0.256 type=other O+ nts=4 GGGG 1:A.DG3,1:A.DG20,1:A.DG15,1:A.DG8 4 glyco-bond=-s-s sugar=---- groove=wnwn planarity=0.367 type=bowl O- nts=4 GGGG 1:A.DG4,1:A.DG19,1:A.DG16,1:A.DG7
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, 4 G-tetrads, INTRA-molecular, with 1 stem
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1 glyco-bond=s-s- sugar=---- groove=wnwn Major-->WC O+ nts=4 GGGG 1:A.DG1,1:A.DG22,1:A.DG13,1:A.DG10 2 glyco-bond=-s-s sugar=-.-- groove=wnwn WC-->Major O- nts=4 GGGG 1:A.DG2,1:A.DG21,1:A.DG14,1:A.DG9 3 glyco-bond=s-s- sugar=---- groove=wnwn Major-->WC O+ nts=4 GGGG 1:A.DG3,1:A.DG20,1:A.DG15,1:A.DG8 4 glyco-bond=-s-s sugar=---- groove=wnwn WC-->Major O- nts=4 GGGG 1:A.DG4,1:A.DG19,1:A.DG16,1:A.DG7 step#1 mm(<>,outward) area=15.20 rise=3.48 twist=17.5 step#2 pp(><,inward) area=17.35 rise=3.64 twist=36.2 step#3 mm(<>,outward) area=16.06 rise=3.47 twist=14.8 strand#1 DNA glyco-bond=s-s- sugar=---- nts=4 GGGG 1:A.DG1,1:A.DG2,1:A.DG3,1:A.DG4 strand#2 DNA glyco-bond=-s-s sugar=-.-- nts=4 GGGG 1:A.DG22,1:A.DG21,1:A.DG20,1:A.DG19 strand#3 DNA glyco-bond=s-s- sugar=---- nts=4 GGGG 1:A.DG13,1:A.DG14,1:A.DG15,1:A.DG16 strand#4 DNA glyco-bond=-s-s sugar=---- nts=4 GGGG 1:A.DG10,1:A.DG9,1:A.DG8,1:A.DG7 |
| 3 stacking diagrams | |
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1 glyco-bond=s-s- sugar=---- groove=wnwn Major-->WC O+ nts=4 GGGG 1:A.DG1,1:A.DG22,1:A.DG13,1:A.DG10 |
|
2 glyco-bond=-s-s sugar=-.-- groove=wnwn WC-->Major O- nts=4 GGGG 1:A.DG2,1:A.DG21,1:A.DG14,1:A.DG9 |
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3 glyco-bond=s-s- sugar=---- groove=wnwn Major-->WC O+ nts=4 GGGG 1:A.DG3,1:A.DG20,1:A.DG15,1:A.DG8 |
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, 4 G-tetrads, 3 loops, INTRA-molecular, UDUD, anti-parallel:chair, 2+2, 4(+Ln+Lw+Ln)
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1 glyco-bond=s-s- sugar=---- groove=wnwn Major-->WC O+ nts=4 GGGG 1:A.DG1,1:A.DG22,1:A.DG13,1:A.DG10 2 glyco-bond=-s-s sugar=-.-- groove=wnwn WC-->Major O- nts=4 GGGG 1:A.DG2,1:A.DG21,1:A.DG14,1:A.DG9 3 glyco-bond=s-s- sugar=---- groove=wnwn Major-->WC O+ nts=4 GGGG 1:A.DG3,1:A.DG20,1:A.DG15,1:A.DG8 4 glyco-bond=-s-s sugar=---- groove=wnwn WC-->Major O- nts=4 GGGG 1:A.DG4,1:A.DG19,1:A.DG16,1:A.DG7 step#1 mm(<>,outward) area=15.20 rise=3.48 twist=17.5 step#2 pp(><,inward) area=17.35 rise=3.64 twist=36.2 step#3 mm(<>,outward) area=16.06 rise=3.47 twist=14.8 strand#1 U DNA glyco-bond=s-s- sugar=---- nts=4 GGGG 1:A.DG1,1:A.DG2,1:A.DG3,1:A.DG4 strand#2 D DNA glyco-bond=-s-s sugar=-.-- nts=4 GGGG 1:A.DG22,1:A.DG21,1:A.DG20,1:A.DG19 strand#3 U DNA glyco-bond=s-s- sugar=---- nts=4 GGGG 1:A.DG13,1:A.DG14,1:A.DG15,1:A.DG16 strand#4 D DNA glyco-bond=-s-s sugar=---- nts=4 GGGG 1:A.DG10,1:A.DG9,1:A.DG8,1:A.DG7 loop#1 type=lateral strands=[#1,#4] nts=2 CC 1:A.DC5,1:A.DC6 loop#2 type=lateral strands=[#4,#3] nts=2 CC 1:A.DC11,1:A.DC12 loop#3 type=lateral strands=[#3,#2] nts=2 CC 1:A.DC17,1:A.DC18 |