Open AccessThe crystal structure of an antiparallel chair-type G-quadruplex formed by Bromo-substituted human telomeric DNA
Author(s) -
Yanyan Geng,
Changdong Liu,
Bo Zhou,
Qixu Cai,
Haitao Miao,
Shi Xiao,
Naining Xu,
Yingying You,
Chun Po Fung,
Rahman Ud Din,
Guang Zhu
Publication year - 2019
Publication title -
nucleic acids research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.008
H-Index - 537
eISSN - 1362-4954
pISSN - 0305-1048
DOI - 10.1093/nar/gkz221
Subject(s) - antiparallel (mathematics) , g quadruplex , stacking , tetrad , biology , dna , guanine , crystal structure , crystallography , molecule , base pair , stereochemistry , folding (dsp implementation) , biophysics , genetics , chemistry , nucleotide , gene , physics , organic chemistry , quantum mechanics , magnetic field , electrical engineering , engineering
Human telomeric guanine-rich DNA, which could adopt different G-quadruplex structures, plays important roles in protecting the cell from recombination and degradation. Although many of these structures were determined, the chair-type G-quadruplex structure remains elusive. Here, we present a crystal structure of the G-quadruplex composed of the human telomeric sequence d[GGGTTAGG8GTTAGGGTTAGG20G] with two dG to 8Br-dG substitutions at positions 8 and 20 with syn conformation in the K+ solution. It forms a novel three-layer chair-type G-quadruplex with two linking trinucleotide loops. Particularly, T5 and T17 are coplanar with two water molecules stacking on the G-tetrad layer in a sandwich-like mode through a coordinating K+ ion and an A6•A18 base pair. While a twisted Hoogsteen A12•T10 base pair caps on the top of G-tetrad core. The three linking TTA loops are edgewise and each DNA strand has two antiparallel adjacent strands. Our findings contribute to a deeper understanding and highlight the unique roles of loop and water molecule in the folding of the G-quadruplex.