Structure and target interaction of a G-quadruplex RNA-aptamer
| Autor: | Marcel Kwiatkowski, Eileen Magbanua, Kristina Szameit, Martin Zacharias, Ulrich Hahn, Hartmut Schlüter, Kira Schamoni, Katharina Berg, Erica Valentini, Dmitri I. Svergun, Isaure Chauvot de Beauchêne, Sven Kruspe, Boris Krichel, Charlotte Uetrecht |
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| Přispěvatelé: | Institute for Biochemistry and Molecular Biology, University of Hamburg, European Molecular Biology Laboratory, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), European Molecular Biology Laboratory [Hamburg] (EMBL) |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Aptamer Computational biology Biology G-quadruplex Aptamers 03 medical and health sciences Nucleic acid structure Binding site Molecular Biology Genetics 030102 biochemistry & molecular biology Microscale thermophoresis molecular modeling RNA [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Cell Biology SAXS G-quadruplexes molecular modelling [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biophysics 030104 developmental biology interleukin-6 receptor Docking (molecular) Nucleic acid protein-RNA interaction [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM] protein- RNA interaction Research Paper |
| Zdroj: | RNA Biology RNA Biology, Taylor & Francis, 2016, 13 (10), pp.973-987. ⟨10.1080/15476286.2016.1212151⟩ |
| ISSN: | 1547-6286 1555-8584 |
| DOI: | 10.1080/15476286.2016.1212151⟩ |
| Popis: | International audience; G-quadruplexes have recently moved into focus of research in nucleic acids, thereby evolving in scientific significance from exceptional secondary structure motifs to complex modulators of gene regulation. Aptamers (nucleic acid based ligands with recognition properties for a specific target) that form Gquadruplexes may have particular potential for therapeutic applications as they combine the characteristics of specific targeting and Gquadruplex mediated stability and regulation. We have investigated the structure and target interaction properties of one such aptamer: AIR-3 and its truncated form AIR-3A. These RNA aptamers are specific for human interleukin-6 receptor (hIL-6R), a key player in inflammatory diseases and cancer, and have recently been exploited for in vitro drug delivery studies. With the aim to resolve the RNA structure, global shape, RNA:protein interaction site and binding stoichiometry, we now investigated AIR-3 and AIR-3A by different methods including RNA structure probing, Small Angle X-ray scattering and microscale thermophoresis. Our findings suggest a broader spectrum of folding species than assumed so far and remarkable tolerance toward different modifications. Mass spectrometry based binding site analysis, supported by molecular modeling and docking studies propose a general Gquadruplex affinity for the target molecule hIL-6R. |
| Databáze: | OpenAIRE |
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