Different loop arrangements of intramolecular human telomeric (3+1) G-quadruplexes in K+ solution.
Intramolecular G-quadruplexes formed by the human telomeric G-rich strand are promising anticancer targets. Here we show that four-repeat human telomeric DNA sequences can adopt two different intramolecular G-quadruplex folds in K+ solution. The two structures contain the (3+1) G-tetrad core, in which three G-tracts are oriented in one direction and the fourth in the opposite direction, with one double-chain-reversal and two edgewise loops, but involve different loop arrangements. This result indicates the robustness of the (3+1) core G-quadruplex topology, thereby suggesting it as an important platform for structure-based drug design. Our data also support the view that multiple human telomeric G-quadruplex conformations coexist in K+ solution. Furthermore, even small changes to flanking sequences can perturb the equilibrium between different coexisting G-quadruplex forms.
Phan
Anh Tuân
AT
Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. phantuan@ntu.edu.sg
Luu
Kim Ngoc
KN
Patel
Dinshaw J
DJ
D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D006147:Guanine / Q000737:chemistry*; D006801:Humans; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D011188:Potassium / Q000737:chemistry*; D012996:Solutions; D016615:Telomere / Q000737:chemistry*
D012996:Solutions; D006147:Guanine; D004247:DNA; D011188:Potassium