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The Functional Role of Loops and Flanking Sequences of G-Quadruplex Aptamer to the Hemagglutinin of Influenza a Virus
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-quadruple...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957560/ https://www.ncbi.nlm.nih.gov/pubmed/33673708 http://dx.doi.org/10.3390/ijms22052409 |
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author | Bizyaeva, Anastasia A. Bunin, Dmitry A. Moiseenko, Valeria L. Gambaryan, Alexandra S. Balk, Sonja Tashlitsky, Vadim N. Arutyunyan, Alexander M. Kopylov, Alexey M. Zavyalova, Elena G. |
author_facet | Bizyaeva, Anastasia A. Bunin, Dmitry A. Moiseenko, Valeria L. Gambaryan, Alexandra S. Balk, Sonja Tashlitsky, Vadim N. Arutyunyan, Alexander M. Kopylov, Alexey M. Zavyalova, Elena G. |
author_sort | Bizyaeva, Anastasia A. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7957560 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79575602021-03-16 The Functional Role of Loops and Flanking Sequences of G-Quadruplex Aptamer to the Hemagglutinin of Influenza a Virus Bizyaeva, Anastasia A. Bunin, Dmitry A. Moiseenko, Valeria L. Gambaryan, Alexandra S. Balk, Sonja Tashlitsky, Vadim N. Arutyunyan, Alexander M. Kopylov, Alexey M. Zavyalova, Elena G. Int J Mol Sci Article 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. MDPI 2021-02-27 /pmc/articles/PMC7957560/ /pubmed/33673708 http://dx.doi.org/10.3390/ijms22052409 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Bizyaeva, Anastasia A. Bunin, Dmitry A. Moiseenko, Valeria L. Gambaryan, Alexandra S. Balk, Sonja Tashlitsky, Vadim N. Arutyunyan, Alexander M. Kopylov, Alexey M. Zavyalova, Elena G. The Functional Role of Loops and Flanking Sequences of G-Quadruplex Aptamer to the Hemagglutinin of Influenza a Virus |
title | The Functional Role of Loops and Flanking Sequences of G-Quadruplex Aptamer to the Hemagglutinin of Influenza a Virus |
title_full | The Functional Role of Loops and Flanking Sequences of G-Quadruplex Aptamer to the Hemagglutinin of Influenza a Virus |
title_fullStr | The Functional Role of Loops and Flanking Sequences of G-Quadruplex Aptamer to the Hemagglutinin of Influenza a Virus |
title_full_unstemmed | The Functional Role of Loops and Flanking Sequences of G-Quadruplex Aptamer to the Hemagglutinin of Influenza a Virus |
title_short | The Functional Role of Loops and Flanking Sequences of G-Quadruplex Aptamer to the Hemagglutinin of Influenza a Virus |
title_sort | functional role of loops and flanking sequences of g-quadruplex aptamer to the hemagglutinin of influenza a virus |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957560/ https://www.ncbi.nlm.nih.gov/pubmed/33673708 http://dx.doi.org/10.3390/ijms22052409 |
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