DSSR-enabled G4 identification/annotation: PDB entry 7ecg
Summary information and primary citation
- PDB-id
- 7ecg
- Class
- DNA
- Method
- X-ray (1.97 Å)
- Summary
- Crystal structure of d(g4c2)2-ba in f222 space group
- Reference
- Geng Y, Liu C, Cai Q, Luo Z, Miao H, Shi X, Xu N, Fung CP, Choy TT, Yan B, Li N, Qian P, Zhou B, Zhu G (2021): "Crystal structure of parallel G-quadruplex formed by the two-repeat ALS- and FTD-related GGGGCC sequence." Nucleic Acids Res., 49, 5881-5890. doi: 10.1093/nar/gkab302.
- Abstract
- The hexanucleotide repeat expansion, GGGGCC (G4C2), within the first intron of the C9orf72 gene is known to be the most common genetic cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The G4C2 repeat expansions, either DNA or RNA, are able to form G-quadruplexes which induce toxicity leading to ALS/FTD. Herein, we report a novel crystal structure of d(G4C2)2 that self-associates to form an eight-layer parallel tetrameric G-quadruplex. Two d(G4C2)2 associate together as a parallel dimeric G-quadruplex which folds into a tetramer via 5'-to-5' arrangements. Each dimer consists of four G-tetrads connected by two CC propeller loops. Especially, the 3'-end cytosines protrude out and form C·C+•C·C+/ C·C•C·C+ quadruple base pair or C•C·C+ triple base pair stacking on the dimeric block. Our work sheds light on the G-quadruplexes adopted by d(G4C2) and yields the invaluable structural details for the development of small molecules to tackle neurodegenerative diseases, ALS and FTD.
- G4 notes
- 8 G-tetrads, 1 G4 helix, 2 G4 stems, 1 G4 coaxial stack, UUUU, parallel, 4+0, coaxial interfaces: 5'/5'
Cartoon-block schematics in six views (download the tarball)
List of 8 G-tetrads
1 glyco-bond=---- sugar=---- groove=---- planarity=0.119 type=planar -- nts=4 GGGG 1:A.DG1,1:A.DG7,3:A.DG1,3:A.DG7 2 glyco-bond=---- sugar=-.-. groove=---- planarity=0.137 type=planar -- nts=4 GGGG 1:A.DG2,1:A.DG8,3:A.DG2,3:A.DG8 3 glyco-bond=---- sugar=---- groove=---- planarity=0.133 type=planar -- nts=4 GGGG 1:A.DG3,1:A.DG9,3:A.DG3,3:A.DG9 4 glyco-bond=---- sugar=---- groove=---- planarity=0.266 type=bowl -- nts=4 GGGG 1:A.DG4,1:A.DG10,3:A.DG4,3:A.DG10 5 glyco-bond=---- sugar=---- groove=---- planarity=0.119 type=planar -- nts=4 GGGG 2:A.DG1,2:A.DG7,4:A.DG1,4:A.DG7 6 glyco-bond=---- sugar=-.-. groove=---- planarity=0.136 type=planar -- nts=4 GGGG 2:A.DG2,2:A.DG8,4:A.DG2,4:A.DG8 7 glyco-bond=---- sugar=---- groove=---- planarity=0.133 type=planar -- nts=4 GGGG 2:A.DG3,2:A.DG9,4:A.DG3,4:A.DG9 8 glyco-bond=---- sugar=---- groove=---- planarity=0.266 type=bowl -- nts=4 GGGG 2:A.DG4,2:A.DG10,4:A.DG4,4:A.DG10
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, 8 G-tetrads, inter-molecular, with 2 stems
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1 glyco-bond=---- sugar=---- groove=---- WC-->Major -- nts=4 GGGG 1:A.DG4,1:A.DG10,3:A.DG4,3:A.DG10 2 glyco-bond=---- sugar=---- groove=---- WC-->Major -- nts=4 GGGG 1:A.DG3,1:A.DG9,3:A.DG3,3:A.DG9 3 glyco-bond=---- sugar=-.-. groove=---- WC-->Major -- nts=4 GGGG 1:A.DG2,1:A.DG8,3:A.DG2,3:A.DG8 4* glyco-bond=---- sugar=---- groove=---- WC-->Major -- nts=4 GGGG 1:A.DG1,1:A.DG7,3:A.DG1,3:A.DG7 5 glyco-bond=---- sugar=---- groove=---- Major-->WC -- nts=4 GGGG 2:A.DG7,2:A.DG1,4:A.DG7,4:A.DG1 6 glyco-bond=---- sugar=.-.- groove=---- Major-->WC -- nts=4 GGGG 2:A.DG8,2:A.DG2,4:A.DG8,4:A.DG2 7 glyco-bond=---- sugar=---- groove=---- Major-->WC -- nts=4 GGGG 2:A.DG9,2:A.DG3,4:A.DG9,4:A.DG3 8 glyco-bond=---- sugar=---- groove=---- Major-->WC -- nts=4 GGGG 2:A.DG10,2:A.DG4,4:A.DG10,4:A.DG4 step#1 mp(<<,backward) area=10.90 rise=3.41 twist=27.9 step#2 mp(<<,backward) area=12.81 rise=3.32 twist=27.0 step#3 mp(<<,backward) area=8.14 rise=3.33 twist=33.4 step#4 mm(<>,outward) area=27.83 rise=3.38 twist=-7.7 step#5 pm(>>,forward) area=8.14 rise=3.33 twist=33.4 step#6 pm(>>,forward) area=12.82 rise=3.32 twist=27.0 step#7 pm(>>,forward) area=10.91 rise=3.41 twist=27.9 strand#1 DNA glyco-bond=-------- sugar=-----.-- nts=8 GGGGGGGG 1:A.DG4,1:A.DG3,1:A.DG2,1:A.DG1,2:A.DG7,2:A.DG8,2:A.DG9,2:A.DG10 strand#2 DNA glyco-bond=-------- sugar=--.----- nts=8 GGGGGGGG 1:A.DG10,1:A.DG9,1:A.DG8,1:A.DG7,2:A.DG1,2:A.DG2,2:A.DG3,2:A.DG4 strand#3 DNA glyco-bond=-------- sugar=-----.-- nts=8 GGGGGGGG 3:A.DG4,3:A.DG3,3:A.DG2,3:A.DG1,4:A.DG7,4:A.DG8,4:A.DG9,4:A.DG10 strand#4 DNA glyco-bond=-------- sugar=--.----- nts=8 GGGGGGGG 3:A.DG10,3:A.DG9,3:A.DG8,3:A.DG7,4:A.DG1,4:A.DG2,4:A.DG3,4:A.DG4 |
| 7 stacking diagrams | |
|
1 glyco-bond=---- sugar=---- groove=---- WC-->Major -- nts=4 GGGG 1:A.DG4,1:A.DG10,3:A.DG4,3:A.DG10 |
|
2 glyco-bond=---- sugar=---- groove=---- WC-->Major -- nts=4 GGGG 1:A.DG3,1:A.DG9,3:A.DG3,3:A.DG9 |
|
3 glyco-bond=---- sugar=-.-. groove=---- WC-->Major -- nts=4 GGGG 1:A.DG2,1:A.DG8,3:A.DG2,3:A.DG8 |
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4* glyco-bond=---- sugar=---- groove=---- WC-->Major -- nts=4 GGGG 1:A.DG1,1:A.DG7,3:A.DG1,3:A.DG7 |
|
5 glyco-bond=---- sugar=---- groove=---- Major-->WC -- nts=4 GGGG 2:A.DG7,2:A.DG1,4:A.DG7,4:A.DG1 |
|
6 glyco-bond=---- sugar=.-.- groove=---- Major-->WC -- nts=4 GGGG 2:A.DG8,2:A.DG2,4:A.DG8,4:A.DG2 |
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7 glyco-bond=---- sugar=---- groove=---- Major-->WC -- nts=4 GGGG 2:A.DG9,2:A.DG3,4:A.DG9,4:A.DG3 |
List of 2 G4-stems
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, 2 loops, inter-molecular, UUUU, parallel, 4+0
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1 glyco-bond=---- sugar=---- groove=---- WC-->Major -- nts=4 GGGG 1:A.DG1,1:A.DG7,3:A.DG1,3:A.DG7 2 glyco-bond=---- sugar=-.-. groove=---- WC-->Major -- nts=4 GGGG 1:A.DG2,1:A.DG8,3:A.DG2,3:A.DG8 3 glyco-bond=---- sugar=---- groove=---- WC-->Major -- nts=4 GGGG 1:A.DG3,1:A.DG9,3:A.DG3,3:A.DG9 4 glyco-bond=---- sugar=---- groove=---- WC-->Major -- nts=4 GGGG 1:A.DG4,1:A.DG10,3:A.DG4,3:A.DG10 step#1 pm(>>,forward) area=8.14 rise=3.33 twist=33.4 step#2 pm(>>,forward) area=12.81 rise=3.32 twist=27.0 step#3 pm(>>,forward) area=10.90 rise=3.41 twist=27.9 strand#1 U DNA glyco-bond=---- sugar=---- nts=4 GGGG 1:A.DG1,1:A.DG2,1:A.DG3,1:A.DG4 strand#2 U DNA glyco-bond=---- sugar=-.-- nts=4 GGGG 1:A.DG7,1:A.DG8,1:A.DG9,1:A.DG10 strand#3 U DNA glyco-bond=---- sugar=---- nts=4 GGGG 3:A.DG1,3:A.DG2,3:A.DG3,3:A.DG4 strand#4 U DNA glyco-bond=---- sugar=-.-- nts=4 GGGG 3:A.DG7,3:A.DG8,3:A.DG9,3:A.DG10 loop#1 type=propeller strands=[#1,#2] nts=2 CC 1:A.DC5,1:A.DC6 loop#2 type=propeller strands=[#3,#4] nts=2 CC 3:A.DC5,3:A.DC6 |
Stem#2, 4 G-tetrads, 2 loops, inter-molecular, UUUU, parallel, 4+0
|
1 glyco-bond=---- sugar=---- groove=---- WC-->Major -- nts=4 GGGG 2:A.DG1,2:A.DG7,4:A.DG1,4:A.DG7 2 glyco-bond=---- sugar=-.-. groove=---- WC-->Major -- nts=4 GGGG 2:A.DG2,2:A.DG8,4:A.DG2,4:A.DG8 3 glyco-bond=---- sugar=---- groove=---- WC-->Major -- nts=4 GGGG 2:A.DG3,2:A.DG9,4:A.DG3,4:A.DG9 4 glyco-bond=---- sugar=---- groove=---- WC-->Major -- nts=4 GGGG 2:A.DG4,2:A.DG10,4:A.DG4,4:A.DG10 step#1 pm(>>,forward) area=8.14 rise=3.33 twist=33.4 step#2 pm(>>,forward) area=12.82 rise=3.32 twist=27.0 step#3 pm(>>,forward) area=10.91 rise=3.41 twist=27.9 strand#1 U DNA glyco-bond=---- sugar=---- nts=4 GGGG 2:A.DG1,2:A.DG2,2:A.DG3,2:A.DG4 strand#2 U DNA glyco-bond=---- sugar=-.-- nts=4 GGGG 2:A.DG7,2:A.DG8,2:A.DG9,2:A.DG10 strand#3 U DNA glyco-bond=---- sugar=---- nts=4 GGGG 4:A.DG1,4:A.DG2,4:A.DG3,4:A.DG4 strand#4 U DNA glyco-bond=---- sugar=-.-- nts=4 GGGG 4:A.DG7,4:A.DG8,4:A.DG9,4:A.DG10 loop#1 type=propeller strands=[#1,#2] nts=2 CC 2:A.DC5,2:A.DC6 loop#2 type=propeller strands=[#3,#4] nts=2 CC 4:A.DC5,4:A.DC6 |
List of 1 G4 coaxial stack
1 G4 helix#1 contains 2 G4 stems: [#1,#2] [5'/5']