Structural basis of sodium-potassium exchange of a human telomeric DNA quadruplex without topological conversion.
Understanding the mechanism of Na(+)/K(+)-dependent spectral conversion of human telomeric G-quadruplex (G4) sequences has been limited not only because of the structural polymorphism but also the lack of sufficient structural information at different stages along the conversion process for one given oligonucleotide. In this work, we have determined the topology of the Na(+) form of Tel23 G4, which is the same hybrid form as the K(+) form of Tel23 G4 despite the distinct spectral patterns in their respective nuclear magnetic resonance (NMR) and circular dichroism spectra. The spectral difference, particularly the well-resolved imino proton NMR signals, allows us to monitor the structural conversion from Na(+) form to K(+) form during Na(+)/K(+) exchange. Time-resolved NMR experiments of hydrogen-deuterium exchange and hybridization clearly exclude involvement of the global unfolding for the fast Na(+)/K(+) spectral conversion. In addition, the K(+) titration monitored by NMR reveals that the Na(+)/K(+) exchange in Tel23 G4 is a two-step process. The addition of K(+) significantly stabilizes the unfolding kinetics of Tel23 G4. These results offer a possible explanation of rapid spectral conversion of Na(+)/K(+) exchange and insight into the mechanism of Na(+)/K(+) structural conversion in human telomeric G4s.
Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei 106, Taiwan, Republic of China, Department of Chemistry, National Taiwan University, Taipei 106, Taiwan, Republic of China, Institute of Biophotonics, National Yang-Ming University, Taipei 112, Taiwan, Republic of China, Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan, Republic of China and Department of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan, Republic of China.
Zi-Fu
ZF
Wang
Ming-Hao
MH
Li
Shang-Te Danny
ST
Hsu
Ta-Chau
TC
Chang
D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D006801:Humans; D019906:Nuclear Magnetic Resonance, Biomolecular; D011188:Potassium / Q000737:chemistry*; D012964:Sodium / Q000737:chemistry*; D016615:Telomere / Q000737:chemistry*
D004247:DNA; D012964:Sodium; D011188:Potassium