Summary information

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
4 G-tetrads, 1 G4 helix, 1 G4 stem, parallel(4+0), UUUU

Base-block schematics in six views

PyMOL session file PDB file View in 3Dmol.js

List of 4 G-tetrads

 1 glyco-bond=---- sugar=---- groove=---- planarity=0.058 type=planar nts=4 GGGG B.DG1,B.DG7,C.DG1,C.DG7
 2 glyco-bond=---- sugar=-.-. groove=---- planarity=0.122 type=planar nts=4 GGGG B.DG2,B.DG8,C.DG2,C.DG8
 3 glyco-bond=---- sugar=---- groove=---- planarity=0.097 type=planar nts=4 GGGG B.DG3,B.DG9,C.DG3,C.DG9
 4 glyco-bond=---- sugar=---- groove=---- planarity=0.217 type=bowl   nts=4 GGGG B.DG4,B.DG10,C.DG4,C.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, 4 G-tetrad layers, inter-molecular, with 1 stem

 1  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG B.DG1,B.DG7,C.DG1,C.DG7
 2  glyco-bond=---- sugar=-.-. groove=---- WC-->Major nts=4 GGGG B.DG2,B.DG8,C.DG2,C.DG8
 3  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG B.DG3,B.DG9,C.DG3,C.DG9
 4  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG B.DG4,B.DG10,C.DG4,C.DG10
  step#1  pm(>>,forward)  area=7.71  rise=3.33 twist=34.1
  step#2  pm(>>,forward)  area=12.78 rise=3.31 twist=27.0
  step#3  pm(>>,forward)  area=11.24 rise=3.39 twist=27.1
  strand#1 DNA glyco-bond=---- sugar=---- nts=4 GGGG B.DG1,B.DG2,B.DG3,B.DG4
  strand#2 DNA glyco-bond=---- sugar=-.-- nts=4 GGGG B.DG7,B.DG8,B.DG9,B.DG10
  strand#3 DNA glyco-bond=---- sugar=---- nts=4 GGGG C.DG1,C.DG2,C.DG3,C.DG4
  strand#4 DNA glyco-bond=---- sugar=-.-- nts=4 GGGG C.DG7,C.DG8,C.DG9,C.DG10

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3 stacking diagrams
 1  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG B.DG1,B.DG7,C.DG1,C.DG7
2 glyco-bond=---- sugar=-.-. groove=---- WC-->Major nts=4 GGGG B.DG2,B.DG8,C.DG2,C.DG8
step#1 pm(>>,forward) area=7.71 rise=3.33 twist=34.1

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 2  glyco-bond=---- sugar=-.-. groove=---- WC-->Major nts=4 GGGG B.DG2,B.DG8,C.DG2,C.DG8
3 glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG B.DG3,B.DG9,C.DG3,C.DG9
step#2 pm(>>,forward) area=12.78 rise=3.31 twist=27.0

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 3  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG B.DG3,B.DG9,C.DG3,C.DG9
4 glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG B.DG4,B.DG10,C.DG4,C.DG10
step#3 pm(>>,forward) area=11.24 rise=3.39 twist=27.1

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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, 4 G-tetrad layers, 1 loops, inter-molecular, UUUU, parallel, parallel(4+0)

 1  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG B.DG1,B.DG7,C.DG1,C.DG7
 2  glyco-bond=---- sugar=-.-. groove=---- WC-->Major nts=4 GGGG B.DG2,B.DG8,C.DG2,C.DG8
 3  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG B.DG3,B.DG9,C.DG3,C.DG9
 4  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG B.DG4,B.DG10,C.DG4,C.DG10
  step#1  pm(>>,forward)  area=7.71  rise=3.33 twist=34.1
  step#2  pm(>>,forward)  area=12.78 rise=3.31 twist=27.0
  step#3  pm(>>,forward)  area=11.24 rise=3.39 twist=27.1
  strand#1  U DNA glyco-bond=---- sugar=---- nts=4 GGGG B.DG1,B.DG2,B.DG3,B.DG4
  strand#2  U DNA glyco-bond=---- sugar=-.-- nts=4 GGGG B.DG7,B.DG8,B.DG9,B.DG10
  strand#3  U DNA glyco-bond=---- sugar=---- nts=4 GGGG C.DG1,C.DG2,C.DG3,C.DG4
  strand#4  U DNA glyco-bond=---- sugar=-.-- nts=4 GGGG C.DG7,C.DG8,C.DG9,C.DG10
  loop#1 type=propeller strands=[#1,#2] nts=2 CC B.DC5,B.DC6

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