Summary information and primary citation
- PDB-id
-
7ech;
DSSR-derived features in text and
JSON formats
- Class
- DNA
- Method
- X-ray (2.38 Å)
- Summary
- Crystal structure of d(g4c2)2-k 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.
