Guanine residues in d(T2AG3) and d(T2G4) form parallel-stranded potassium cation stabilized G-quadruplexes with anti glycosidic torsion angles in solution.
We report below on proton NMR studies of the G-quadruplex structure formed by the human telomere sequence d(T2AG3) and the tetrahymena telomere sequence d(T2G4) in K cation containing solution. We observe well-resolved proton NMR spectra corresponding to a G-quadruplex monomer conformation predominant at 50 mM K cation concentration and a G-quadruplex dimer conformation predominant at 300 mM K cation concentration. By contrast, d(T2AG3T) and d(T2G4T) form only the G-quadruplex monomer structures independent of K cation concentration as reported previously [Sen, D., & Gilbert, W. (1992) Biochemistry 31, 65-70]. We detect well-resolved resonances for the exchangeable guanine imino and amino protons involved in G-tetrad formation with the hydrogen-bonded and exposed amino protons separated by up to 3.5 ppm. The observed NOEs between the amino and H8 protons on adjacent guanines within individual G-tetrads support the Hoogsteen pairing alignment around the tetrad. The imino protons of the internal G-tetrads exchange very slowly with solvent H2O in the d(T2AG3) and d(T2G4) quadruplexes. The nature and intensity of the observed NOE patterns establish formation of parallel-stranded right-handed G-quadruplexes with all anti guanine glycosidic torsion angles. A model for the parallel-stranded G-quadruplex is proposed which is consistent with the experimental NOE data on the d(T2AG3) and d(T2G4) quadruplexes in solution.(ABSTRACT TRUNCATED AT 250 WORDS)
Wang
Y
Y
Department of Biochemistry and Molecular Biophysics, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
Patel
D J
DJ
D001483:Base Sequence; D006027:Glycosides; D006147:Guanine; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D012996:Solutions; D013329:Structure-Activity Relationship
D006027:Glycosides; D009838:Oligodeoxyribonucleotides; D012996:Solutions; D006147:Guanine