Unveiling the unusual i-motif-derived architecture of a DNA aptamer exhibiting high affinity for influenza A virus

IF 16.6 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Nucleic Acids Research Pub Date : 2025-01-07 DOI:10.1093/nar/gkae1282

Vladimir Tsvetkov, Bartomeu Mir, Rugiya Alieva, Alexander Arutyunyan, Ilya Oleynikov, Roman Novikov, Elizaveta Boravleva, Polina Kamzeeva, Timofei Zatsepin, Andrey Aralov, Carlos González, Elena Zavyalova

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引用次数: 0

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.

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揭示了对甲型流感病毒具有高亲和力的DNA适体的不同寻常的i基序衍生结构

非典型核酸结构通过与蛋白质的选择性相互作用在细胞过程中发挥重要作用。虽然人们对天然和人工g -四重复合物进行了广泛的研究，但对i基序的功能仍知之甚少。本研究研究了人工适体BV42，它与甲型流感病毒血凝素结合强烈，即使在中性ph下也能保持其i基序结构。然而，BV42的构象异质性阻碍了详细的结构分析。BV42的分子动力学模拟和化学修饰帮助我们确定了一个潜在的结合位点，允许对适体进行重新设计，以消除构象多样性，同时保持结合亲和力。核磁共振波谱证实了i-motif/双工结与附近的三胞嘧啶环。本研究强调了功能性i-motif的独特结构特征及其在靶标分子识别中的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nucleic Acids Research 生物-生化与分子生物学

CiteScore

27.10

自引率

4.70%

发文量

1057

审稿时长

2 months

期刊介绍： Nucleic Acids Research (NAR) is a scientific journal that publishes research on various aspects of nucleic acids and proteins involved in nucleic acid metabolism and interactions. It covers areas such as chemistry and synthetic biology, computational biology, gene regulation, chromatin and epigenetics, genome integrity, repair and replication, genomics, molecular biology, nucleic acid enzymes, RNA, and structural biology. The journal also includes a Survey and Summary section for brief reviews. Additionally, each year, the first issue is dedicated to biological databases, and an issue in July focuses on web-based software resources for the biological community. Nucleic Acids Research is indexed by several services including Abstracts on Hygiene and Communicable Diseases, Animal Breeding Abstracts, Agricultural Engineering Abstracts, Agbiotech News and Information, BIOSIS Previews, CAB Abstracts, and EMBASE.