Structure of two intramolecular G-quadruplexes formed by natural human telomere sequences in K+ solution.
Intramolecular G-quadruplexes formed by human telomere sequences are attractive anticancer targets. Recently, four-repeat human telomere sequences have been shown to form two different intramolecular (3 + 1) G-quadruplexes in K(+) solution (Form 1 and Form 2). Here we report on the solution structures of both Form 1 and Form 2 adopted by natural human telomere sequences. Both structures contain the (3 + 1) G-tetrad core with one double-chain-reversal and two edgewise loops, but differ in the successive order of loop arrangements within the G-quadruplex scaffold. Our results provide the structural details at the two ends of the G-tetrad core in the context of natural sequences and information on different loop conformations. This structural information might be important for our understanding of telomere G-quadruplex structures and for anticancer drug design targeted to such scaffolds.
Phan
Anh Tuân
AT
Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. phantuan@ntu.edu.sg
Kuryavyi
Vitaly
V
Luu
Kim Ngoc
KN
Patel
Dinshaw J
DJ
D001483:Base Sequence; D002412:Cations; D004247:DNA / Q000737:chemistry; D054856:G-Quadruplexes; D006801:Humans; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D011188:Potassium / Q000737:chemistry; D012091:Repetitive Sequences, Nucleic Acid; D012996:Solutions; D016615:Telomere / Q000737:chemistry*
D002412:Cations; D012996:Solutions; D004247:DNA; D011188:Potassium