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Four Steps for Revealing and Adjusting the 3D Structure of Aptamers in Solution by Small-Angle X-ray Scattering and Computer Simulation Full article

Journal Analytical and Bioanalytical Chemistry
ISSN: 1618-2642 , E-ISSN: 1618-2650
Output data Year: 2019, Volume: 411, Number: 25, Pages: 6723-6732 Pages count : 10 DOI: 10.1007/s00216-019-02045-0
Tags Aptamer . Thrombin . Three-dimensional structure . Small-angle X-ray scattering . Molecular modeling
Authors Tomilin Felix N. 1,2 , Moryachkov Roman 1,3 , Shchugoreva Irina 2,3 , Zabluda Vladimir N. 1 , Peters Georgy 4 , Platunov Mikhail 1 , Spiridonova Vera 5 , Melnichuk Anastasia 5 , Atrokhova Anastasia 5 , Zamay Sergey S. 1,3 , Ovchinnikov Sergey G. 1,2 , Zamay Galina S. 3,6 , Sokolov Alexey 1,2 , Zamay Tatiana N. 3,6 , Berezovski Maxim V. 7 , Kichkailo Anna S. 3,6
Affiliations
1 Kirensky Institute of Physics, Federal Research Center KSC Siberian Branch Russian Academy of Sciences, 50/38 Akademgorodok, Krasnoyarsk 660036, Russia
2 Siberian Federal University, 79 Svobodny pr., Krasnoyarsk 660041, Russia
3 Federal Research Center “Krasnoyarsk Science Center” Siberian Branch of the Russian Academy of Sciences, 50, Akademgorodok, Krasnoyarsk 660036, Russia
4 NRC Kurchatov Institute, 1, Academic Kurchatov Square, Moscow 123182, Russia
5 A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 1/40 Leninskie Gory, Moscow 119992, Russia
6 Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia
7 Department of Chemistry and Biomolecular Sciences, University of Ottawa, 10 Marie-Curie, Ottawa, Ontario K1N6N5, Canada

Abstract: Nucleic acid (NA) aptamers bind to their targets with high affinity and selectivity. The three-dimensional (3D) structures of aptamers play a major role in these non-covalent interactions. Here, we use a four-step approach to determine a true 3D structure of aptamers in solution using small-angle X-ray scattering (SAXS) and molecular structure restoration (MSR). The approach consists of (i) acquiring SAXS experimental data of an aptamer in solution, (ii) building a spatial distribution of the molecule's electron density using SAXS results, (iii) constructing a 3D model of the aptamer from its nucleotide primary sequence and secondary structure, and (iv) comparing and refining the modeled 3D structures with the experimental SAXS model. In the proof-of-principle we analyzed the 3D structure of RE31 aptamer to thrombin in a native free state at different temperatures and validated it by circular dichroism (CD). The resulting 3D structure of RE31 has the most energetically favorable conformation and the same elements such as a B-form duplex, non-complementary region, and two G-quartets which were previously reported by X-ray diffraction (XRD) from a single crystal. More broadly, this study demonstrates the complementary approach for constructing and adjusting the 3D structures of aptamers, DNAzymes, and ribozymes in solution, and could supply new opportunities for developing functional nucleic acids.
Cite: Tomilin F.N. , Moryachkov R. , Shchugoreva I. , Zabluda V.N. , Peters G. , Platunov M. , Spiridonova V. , Melnichuk A. , Atrokhova A. , Zamay S.S. , Ovchinnikov S.G. , Zamay G.S. , Sokolov A. , Zamay T.N. , Berezovski M.V. , Kichkailo A.S.
Four Steps for Revealing and Adjusting the 3D Structure of Aptamers in Solution by Small-Angle X-ray Scattering and Computer Simulation
Analytical and Bioanalytical Chemistry. 2019. V.411. N25. P.6723-6732. DOI: 10.1007/s00216-019-02045-0 WOS Scopus РИНЦ ANCAN OpenAlex
Dates:
Submitted: Apr 11, 2019
Accepted: Jul 22, 2019
Published online: Aug 8, 2019
Published print: Oct 1, 2019
Identifiers:
Web of science: WOS:000486030400022
Scopus: 2-s2.0-85070260700
Elibrary: 41623829
Chemical Abstracts: 2019:1550555
Chemical Abstracts (print): 171:434504
OpenAlex: W2967612380
Citing:
DB Citing
Web of science 12
Scopus 14
OpenAlex 15
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