Structure of the human telomere in K+ solution: an intramolecular (3 + 1) G-quadruplex scaffold.
We present the intramolecular G-quadruplex structure of human telomeric DNA in physiologically relevant K(+) solution. This G-quadruplex, whose (3 + 1) topology differs from folds reported previously in Na(+) solution and in a K(+)-containing crystal, involves the following: one anti.syn.syn.syn and two syn.anti.anti.anti G-tetrads; one double-chain reversal and two edgewise loops; three G-tracts oriented in one direction and the fourth in the opposite direction. The topological characteristics of this (3 + 1) G-quadruplex scaffold should provide a unique platform for structure-based anticancer drug design targeted to human telomeric DNA.
Luu
Kim Ngoc
KN
Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Phan
Anh Tuân
AT
Kuryavyi
Vitaly
V
Lacroix
Laurent
L
Patel
Dinshaw J
DJ
D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D006147:Guanine / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011188:Potassium / Q000737:chemistry*; D012996:Solutions / Q000737:chemistry; D016615:Telomere / Q000737:chemistry*
D012996:Solutions; D006147:Guanine; D004247:DNA; D011188:Potassium