Chemistry Department, Lomonosov Moscow State University, 119991 Moscow, Russia.
Chumakov Federal Scientific Centre for Research and Development of Immune and Biological Products RAS, 108819 Moscow, Russia.
Int J Mol Sci. 2021 Feb 27;22(5):2409. doi: 10.3390/ijms22052409.
Nucleic acid aptamers are generally accepted as promising elements for the specific and high-affinity binding of various biomolecules. It has been shown for a number of aptamers that the complexes with several related proteins may possess a similar affinity. An outstanding example is the G-quadruplex DNA aptamer RHA0385, which binds to the hemagglutinins of various influenza A virus strains. These hemagglutinins have homologous tertiary structures but moderate-to-low amino acid sequence identities. Here, the experiment was inverted, targeting the same protein using a set of related, parallel G-quadruplexes. The 5'- and 3'-flanking sequences of RHA0385 were truncated to yield parallel G-quadruplex with three propeller loops that were 7, 1, and 1 nucleotides in length. Next, a set of minimal, parallel G-quadruplexes with three single-nucleotide loops was tested. These G-quadruplexes were characterized both structurally and functionally. All parallel G-quadruplexes had affinities for both recombinant hemagglutinin and influenza virions. In summary, the parallel G-quadruplex represents a minimal core structure with functional activity that binds influenza A hemagglutinin. The flanking sequences and loops represent additional features that can be used to modulate the affinity. Thus, the RHA0385-hemagglutinin complex serves as an excellent example of the hypothesis of a core structure that is decorated with additional recognizing elements capable of improving the binding properties of the aptamer.
核酸适体被普遍认为是能够特异性和高亲和力结合各种生物分子的有前途的元素。已经有许多适体证明，与几种相关蛋白质形成的复合物可能具有相似的亲和力。一个突出的例子是 G-四链体 DNA 适体 RHA0385，它与多种流感 A 病毒株的血凝素结合。这些血凝素具有同源的三级结构，但氨基酸序列的同一性中等至较低。在这里，实验进行了反转，使用一组相关的平行 G-四链体针对相同的蛋白质。RHA0385 的 5'-和 3'-侧翼序列被截断，生成具有三个螺旋桨环的平行 G-四链体，长度分别为 7、1 和 1 个核苷酸。接下来，测试了一组具有三个单核苷酸环的最小平行 G-四链体。这些 G-四链体在结构和功能上都进行了表征。所有平行 G-四链体都与重组血凝素和流感病毒粒子具有亲和力。总之，平行 G-四链体代表了一种具有功能活性的最小核心结构，它能与流感 A 血凝素结合。侧翼序列和环代表了可以用来调节亲和力的附加特征。因此，RHA0385-血凝素复合物是核心结构假说的一个极好例子，该假说认为核心结构被能够改善适体结合特性的附加识别元件所修饰。
