Effects of Salt on the Stability of a G-Quadruplex from the Human c-MYC Promoter

In an atmosphere of potassium ions, a modified c-MYC NHE III1 sequence with two G-to-T mutations (MYC22-G14T/G23T) forms a highly stable parallel-stranded G-quadruplex. The G-quadruplex exhibits a steady increase in its melting temperature, TM, with an increase in the concentration of the stabilizing cation K+. On the other hand, an increase in the concentration of nonstabilizing Cs+ or TMA+ cations at a constant concentration of K+ causes a sharp decline in TM followed by a leveling off at ∼200 mM Cs+ or TMA+. At 51 °C and 600 μM K+, an increase in Cs+ concentration from 0 to 800 mM leads to a complete unfolding of the G-quadruplex. These observations are consistent with the picture in which more counterions accumulate in the vicinity of the unfolded state of MYC22-G14T/G23T (nonspecific ion binding) than in that of the G-quadruplex state. We estimate that the unfolded state condenses one extra counterion compared to the G-quadruplex state. Taken together with our earlier results, our data suggest that s...