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

Jamie M. Dettler, Robert Buscaglia, Jing Jing Cui, Derek Cashman, Meredith Blynn, Edwin A. Lewis

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

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 T m values of 38.1, 46.6, and 49.5°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.

Original languageEnglish (US)
Pages (from-to)561-567
Number of pages7
JournalBiophysical Journal
Volume99
Issue number2
DOIs
StatePublished - Jul 21 2010
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics

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