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T.T pair intercalation and duplex interconversion within i-motif tetramers.

Jean Louis Leroy1

  • 1Laboratoire de RMN à Haut Champ, Centre National de la Recherche Scientifique, Institut de Chimie des Substances Naturelles, Ave de la Terrasse Bat 27, 91198 Gif-sur-Yvette, France.

Journal of Molecular Biology
|October 1, 2003
PubMed
Summary

Investigating three i-motif tetramers using NMR, this study reveals distinct structural conformations and dynamics. The symmetric i-motif conformation increases with linker length, influencing structural interconversions and base-pairing kinetics.

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Area of Science:

  • Biochemistry
  • Structural Biology
  • Molecular Biophysics

Background:

  • The i-motif is a four-stranded DNA structure formed by parallel duplexes linked by hemi-protonated C.C(+) pairs.
  • Understanding i-motif structural dynamics and base-pairing is crucial for its biological roles and potential applications.

Purpose of the Study:

  • To investigate the structure, base-pair opening kinetics, and internal motions of three i-motif tetramers: [d(5mCCTCnTCC)](4) (n=1, 2, 3).
  • To elucidate the conformational heterogeneity and dynamic interconversion mechanisms within these i-motif structures.

Main Methods:

  • Nuclear Magnetic Resonance (NMR) spectroscopy was employed to study the structure and dynamics.
  • Analysis of base-pair opening kinetics and internal motions was performed using NMR data.

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Main Results:

  • Three i-motif tetramers ([d(5mCCTCnTCC)](4), n=1, 2, 3) were found to adopt distinct conformations, involving either base-paired or unstacked thymidine bases.
  • The proportion of a fully symmetric conformer increased with the linker length (n), reaching over 95% for n=3.
  • Structural interconversion between symmetric and asymmetric conformations was observed, triggered by the opening/closing of specific thymidine bases, with dynamics varying based on linker length.

Conclusions:

  • The study demonstrates that i-motif tetramers can exist in multiple conformations, influenced by linker length and specific base interactions.
  • The observed structural dynamics, including duplex interconversion, provide insights into the flexibility and adaptability of the i-motif structure.
  • The findings contribute to a deeper understanding of the structural basis for i-motif formation and function.