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A non-B DNA binding peptidomimetic channel alters cellular functions

Author

Listed:
  • Raj Paul

    (Indian Association for the Cultivation of Science)

  • Debasish Dutta

    (Indian Association for the Cultivation of Science)

  • Titas Kumar Mukhopadhyay

    (Indian Association for the Cultivation of Science)

  • Diana Müller

    (Center for Biomolecular Magnetic Resonance (BMRZ), Goethe, University Frankfurt, Max-von-Laue Strasse 7)

  • Binayak Lala

    (Indian Association for the Cultivation of Science)

  • Ayan Datta

    (Indian Association for the Cultivation of Science)

  • Harald Schwalbe

    (Center for Biomolecular Magnetic Resonance (BMRZ), Goethe, University Frankfurt, Max-von-Laue Strasse 7)

  • Jyotirmayee Dash

    (Indian Association for the Cultivation of Science)

Abstract

DNA binding transcription factors possess the ability to interact with lipid membranes to construct ion-permeable pathways. Herein, we present a thiazole-based DNA binding peptide mimic TBP2, which forms transmembrane ion channels, impacting cellular ion concentration and consequently stabilizing G-quadruplex DNA structures. TBP2 self-assembles into nanostructures, e.g., vesicles and nanofibers and facilitates the transportation of Na+ and K+ across lipid membranes with high conductance (~0.6 nS). Moreover, TBP2 exhibits increased fluorescence when incorporated into the membrane or in cellular nuclei. Monomeric TBP2 can enter the lipid membrane and localize to the nuclei of cancer cells. The coordinated process of time-dependent membrane or nuclear localization of TBP2, combined with elevated intracellular cation levels and direct G-quadruplex (G4) interaction, synergistically promotes formation and stability of G4 structures, triggering cancer cell death. This study introduces a platform to mimic and control intricate biological functions, leading to the discovery of innovative therapeutic approaches.

Suggested Citation

  • Raj Paul & Debasish Dutta & Titas Kumar Mukhopadhyay & Diana Müller & Binayak Lala & Ayan Datta & Harald Schwalbe & Jyotirmayee Dash, 2024. "A non-B DNA binding peptidomimetic channel alters cellular functions," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49534-0
    DOI: 10.1038/s41467-024-49534-0
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    References listed on IDEAS

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    1. Manish Debnath & Sandipan Chakraborty & Y. Pavan Kumar & Ritapa Chaudhuri & Biman Jana & Jyotirmayee Dash, 2020. "Ionophore constructed from non-covalent assembly of a G-quadruplex and liponucleoside transports K+-ion across biological membranes," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
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