Unveiling the unusual i-motif-derived architecture of a DNA aptamer exhibiting high affinity for influenza A virus
Non-canonical nucleic acid structures play significant roles in cellular processes through selective interactions with proteins. While both natural and artificial G-quadruplexes have been extensively studied, the functions of i-motifs remain less understood. This study investigates the artificial aptamer BV42, which binds strongly to influenza A virus hemagglutinin and unexpectedly retains its i-motif structure even at neutral pH. However, BV42 conformational heterogeneity hinders detailed structural analysis. Molecular dynamics simulations and chemical modifications of BV42 helped us to identify a potential binding site, allowing for aptamer redesign to eliminate the conformational diversity while retaining binding affinity. Nuclear magnetic resonance spectroscopy confirmed the i-motif/duplex junction with the three-cytosine loop nearby. This study highlights the unique structural features of the functional i-motif and its role in molecular recognition of the target.
Authors
- Timofei S. Zatsepin (ORCID: https://orcid.org/0000-0003-0030-9174)
- Elena Zavyalova (ORCID: https://orcid.org/0000-0001-5260-1973)
- Andrey V. Aralov (ORCID: https://orcid.org/0000-0003-3268-2352)
- Роман А. Новиков (ORCID: https://orcid.org/0000-0002-3740-7424)
- Bartomeu Mir (ORCID: https://orcid.org/0000-0001-6613-9601)
- Vladimir B. Tsvetkov (ORCID: https://orcid.org/0000-0003-0494-3332)
- Rugiya Alieva
- Ilya Oleynikov (ORCID: https://orcid.org/0000-0002-5277-1945)
- Polina N. Kamzeeva
- Carlos González (ORCID: https://orcid.org/0000-0001-8796-1282)
- Elizaveta Yu. Boravleva (ORCID: https://orcid.org/0000-0001-8491-4640)
- Alexander M. Arutyunyan
Institutions
- Engelhardt Institute of Molecular Biology (RU)
- Russian Academy of Sciences (RU)
- Sechenov University (RU)
- Lomonosov Moscow State University (RU)
- Institute of Bioorganic Chemistry (RU)
- Federal Research and Clinical Center of Physical-Chemical Medicine named after Y.M. Lopukhin (RU)
- Chumakov Institute of Poliomyelitis and Viral Encephalitides (RU)
- Moscow State University (TJ)
Publication Details
- Journal
- Nucleic Acids Research
- Published
- 2024-12-13
- DOI
- https://doi.org/10.1093/nar/gkae1282
- Citations
- 11
- Primary Topic
- Advanced biosensing and bioanalysis techniques
- Type
- article
- Field-Weighted Citation Impact
- 2.57
Funders
- I.M. Sechenov First Moscow State Medical University
- Ministry of Health of the Russian Federation