Energetics and kinetics of a conformational switch in G-quadruplex DNA.
Circular dichroism and differential scanning calorimetry were used to determine the energetics of the conformational switch of the human telomere quadruplex formed by the sequence d[AGGG(TTAGGG)3] between the sodium basket form and the potassium hybrid form. The energy barrier separating the two conformations was found to be modest, only 1.4-2.4 kcal mol(-1). The kinetics of exchange of bound K+ for Na+ cations and the concomitant conformational switch was assessed by measuring time-dependent changes in the circular dichroism spectrum accompanying the cation exchange reaction. The time course of these changes was found to consist of three distinct kinetic processes: a rapid phase that was complete in less than 5 ms followed by two slower phases with relaxation times of 40-50 s and 600-800 s at 25 degrees C and pH 7.0. We interpret these kinetics in terms of a model in which the bound Na+ cations are rapidly replaced by K+ followed by relatively slow structural rearrangements to generate the final K(+)-bound product(s). Circular dichroism studies showed that addition of the porphyrin TmPyP4 promoted conversion of the basket to the hybrid form. The kinetics of the TmPyP4-induced conformational change were the same as those observed for the cation exchange reaction.
Gray
Robert D
RD
James Graham Brown Cancer Center, University of Louisville, 529 South Jackson Street, Louisville, Kentucky 40202, USA.
Li
Jing
J
Chaires
Jonathan B
JB
D001703:Biophysics / Q000379:methods*; D002152:Calorimetry, Differential Scanning / Q000379:methods; D002412:Cations; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D007700:Kinetics; D015233:Models, Statistical; D008968:Molecular Conformation; D011188:Potassium / Q000737:chemistry; D012964:Sodium / Q000737:chemistry; D016615:Telomere / Q000737:chemistry; D013696:Temperature; D013816:Thermodynamics
D002412:Cations; D004247:DNA; D012964:Sodium; D011188:Potassium
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