Structural basis for high-affinity fluorophore binding and activation by RNA Mango
| Autor: | Robert J. Trachman, Shanker Shyam S. Panchapakesan, Adrian R. Ferré-D'Amaré, Natalia A Demeshkina, Peter J. Unrau, Sunny C. Y. Jeng, Matthew W.L. Lau |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Fluorophore Aptamer Ligands 010402 general chemistry 01 natural sciences Article 03 medical and health sciences chemistry.chemical_compound Benzothiazoles Binding site Molecular Biology Fluorescent Dyes Binding Sites Ligand RNA Cell Biology Fluorescence 0104 chemical sciences 030104 developmental biology Biochemistry chemistry Quinolines Linker Macromolecule |
| Zdroj: | Nature chemical biology |
| ISSN: | 1552-4469 1552-4450 |
| Popis: | Genetically encoded fluorescent protein tags revolutionized proteome studies, while the lack of intrinsically fluorescent RNAs has hindered transcriptome exploration. Among several RNA-fluorophore complexes that potentially address this problem, RNA Mango has an exceptionally high affinity for its thiazole orange (TO)-derived fluorophore, TO1-Biotin (Kd ~3 nM), and in complex with related ligands, is one of the most red-shifted fluorescent macromolecular tags known. To elucidate how this small aptamer exhibits such properties, which make it well suited for studying low-copy cellular RNAs, we determined its 1.7 Å resolution co-crystal structure. Unexpectedly, the entire ligand, including TO, biotin, and the linker connecting them, abuts one of the near-planar faces of the three-tiered G-quadruplex. The two heterocycles of TO are held in place by two loop adenines and make a 45° angle with respect to each other. Minimizing this angle would increase quantum yield and further improve this tool for in vivo RNA visualization. Graphical Abstract |
| Databáze: | OpenAIRE |
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