Structural highlights
Publication Abstract from PubMedSeveral turn-on RNA aptamers that activate small-molecule fluorophores have been selected in vitro. Among these, the ~30 nucleotide Mango-III is notable because it binds the thiazole orange derivative TO1-Biotin with high affinity and fluoresces brightly (quantum yield 0.55). Uniquely among related aptamers, Mango-III exhibits biphasic thermal melting, characteristic of molecules with tertiary structure. We report crystal structures of TO1-Biotin complexes of Mango-III, a structure-guided mutant Mango-III(A10U), and a functionally reselected mutant iMango-III. The structures reveal a globular architecture arising from an unprecedented pseudoknot-like connectivity between a G-quadruplex and an embedded non-canonical duplex. The fluorophore is restrained into a planar conformation by the G-quadruplex, a lone, long-range trans Watson-Crick pair (whose A10U mutation increases quantum yield to 0.66), and a pyrimidine perpendicular to the nucleobase planes of those motifs. The improved iMango-III and Mango-III(A10U) fluoresce ~50% brighter than enhanced green fluorescent protein, making them suitable tags for live cell RNA visualization. Structure and functional reselection of the Mango-III fluorogenic RNA aptamer.,Trachman RJ 3rd, Autour A, Jeng SCY, Abdolahzadeh A, Andreoni A, Cojocaru R, Garipov R, Dolgosheina EV, Knutson JR, Ryckelynck M, Unrau PJ, Ferre-D'Amare AR Nat Chem Biol. 2019 May;15(5):472-479. doi: 10.1038/s41589-019-0267-9. Epub 2019 , Apr 15. PMID:30992561[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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