5OPH

G-quadruplex structure of DNA oligonucleotide containing GGGGCC repeats linked to ALS and FTD

Summary for 5OPH

• Entry DOI: 10.2210/pdb5oph/pdb
• NMR Information: BMRB: 34168
• Descriptor: DNA (5'-D(*GP*GP*GP*GP*CP*CP*GP*GP*GP*GP*CP*CP*GP*GP*GP*GP*CP*CP*GP*GP*(BGM)P*G)-3') (1 entity in total)
• Functional Keywords: g-quadruplex, dna, nucelar magnetic resonance, k+ solution, antiparallel, four g-quartets, edgewise loops, stacking, ggggcc-repat, als and ftd, neurodegenerative disorders, repetitive sequences, nucleic acid, 8br-dg, modified residue
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 7036.32

Authors

Brcic, J.,Plavec, J. (deposition date: 2017-08-09, release date: 2018-08-29, Last modification date: 2024-05-15)

Primary citation

Brcic, J.,Plavec, J.
NMR structure of a G-quadruplex formed by four d(G4C2) repeats: insights into structural polymorphism.
Nucleic Acids Res., 46:11605-11617, 2018

PubMed Abstract: Most frequent genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), is a largely increased number of d(G4C2)n•(G2C4)n repeats located in the non-coding region of C9orf72 gene. Non-canonical structures, including G-quadruplexes, formed within expanded repeats have been proposed to drive repeat expansion and pathogenesis of ALS and FTD. Oligonucleotide d[(G4C2)3G4], which represents the shortest oligonucleotide model of d(G4C2) repeats with the ability to form a unimolecular G-quadruplex, forms two major G-quadruplex structures in addition to several minor species which coexist in solution with K+ ions. Herein, we used solution-state NMR to determine the high-resolution structure of one of the major G-quadruplex species adopted by d[(G4C2)3G4]. Structural characterization of the G-quadruplex named AQU was facilitated by a single substitution of dG with 8Br-dG at position 21 and revealed an antiparallel fold composed of four G-quartets and three lateral C-C loops. The G-quadruplex exhibits high thermal stability and is favored kinetically and under slightly acidic conditions. An unusual structural element distinct from a C-quartet is observed in the structure. Two C•C base pairs are stacked on the nearby G-quartet and are involved in a dynamic equilibrium between symmetric N3-amino and carbonyl-amino geometries and protonated C+•C state.

PubMed: 30277522
DOI: 10.1093/nar/gky886

Experimental method

SOLUTION NMR