Guanine residues in d (T2AG3) and d (T2G4) form parallel-stranded potassium cation stabilized G-quadruplexes with anti glycosidic torsion angles in solution

Y Wang, DJ Patel - Biochemistry, 1992 - ACS Publications
Biochemistry, 1992ACS Publications
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 …
Abstract
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 inG-tetrad formation with the hydrogen-bondedand exposed amino protons separated by up to 3.5 ppm. The observed NOEs between the amino and H8 protons on adjacent guanines within individualG-tetrads support the Hoogsteen pairing alignment around the tetrad. The imino protons of the internal G-tetrads exchange very slowly with solvent H20 in the d (T2AG2) 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 (T2AG2) and d (T2G4) quadruplexes in solution. These results are in contrast to earlier studies on d (G „TmG „) sequences where the structures of the monovalent cation stabilized G-quadruplex exhibit alternating G (syn)-G (anti) glycosidic torsion angles along individual strands in solution [Wang, Y., de los Santos, C., Gao, X., Greene, K., Live, D., & Patel, D. J.(1991) J. Mol. Biol. 222, 819-832] and in the crystalline state [Kang, C. H., Zhang, X., Ratliff, R., Moyzis, R., & Rich, A.(1992) Nature 356, 126-131].
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