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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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.
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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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