Unveiling the unusual i-motif-derived architecture of a DNA aptamer exhibiting high affinity for influenza A virus
В.Б. Цветков, Bartomeu Mir, Rugiya Alieva, Alexander M. Arutyunyan, Ilya Oleynikov, Роман А. Новиков, Elizaveta Boravleva, Polina N. Kamzeeva, Timofei S. Zatsepin, Andrey V. Aralov, Carlos González, Elena Zavyalova
Abstract
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.