Biophysical characterization of an ensemble of intramolecular i-motifs formed by the human c-MYC NHE III1 P1 promoter mutant sequence.

Biophysical Journal
Jamie M DettlerEdwin A Lewis

Abstract

i-Motif-forming sequences are present in or near the regulatory regions of >40% of all genes, including known oncogenes. We report here the results of a biophysical characterization and computational study of an ensemble of intramolecular i-motifs that model the polypyrimidine sequence in the human c-MYC P1 promoter. Circular dichroism results demonstrate that the mutant sequence (5'-CTT TCC TAC CCTCCC TAC CCT AA-3') can adopt multiple "i-motif-like," classical i-motif, and single-stranded structures as a function of pH. The classical i-motif structures are predominant in the pH range 4.2-5.2. The "i-motif-like" and single-stranded structures are the most significant species in solution at pH higher and lower, respectively, than that range. Differential scanning calorimetry results demonstrate an equilibrium mixture of at least three i-motif folded conformations with Tm values of 38.1, 46.6, and 49.5 degrees C at pH 5.0. The proposed ensemble of three folded conformations includes the three lowest-energy conformations obtained by computational modeling and two folded conformers that were proposed in a previous NMR study. The NMR study did not report the most stable conformer found in this study.

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Citations

Oct 18, 2013·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jingjing CuiEdwin A Lewis
Jan 15, 2013·Photochemistry and Photobiology·Jungkweon Choi, Tetsuro Majima
Mar 16, 2011·Biophysical Journal·Jamie M DettlerEdwin A Lewis
Nov 26, 2014·Journal of the American Chemical Society·Guillaume Mata, Nathan W Luedtke
Sep 3, 2011·Journal of the American Chemical Society·Jungkweon ChoiTetsuro Majima
Jun 11, 2015·Physical Chemistry Chemical Physics : PCCP·Taiga Fujii, Naoki Sugimoto
Dec 11, 2014·Nature Communications·Kasturi BanerjeeJohn W Cave
Sep 9, 2011·Chemical Society Reviews·Jungkweon Choi, Tetsuro Majima
Jun 3, 2015·Chembiochem : a European Journal of Chemical Biology·Laurie LannesHarald Schwalbe
Jan 18, 2018·Physical Chemistry Chemical Physics : PCCP·A D ProtopopovaG E Pozmogova
Mar 7, 2020·Epigenetics & Chromatin·Wenhuan TangQili Feng
Jan 23, 2018·Journal of the American Chemical Society·Lutan LiuTigran V Chalikian

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