Large Stokes shift fluorescence activation in an RNA aptamer by intermolecular proton transfer to guanine
Please always quote using this URN: urn:nbn:de:bvb:20-opus-254527
- Fluorogenic RNA aptamers are synthetic functional RNAs that specifically bind and activate conditional fluorophores. The Chili RNA aptamer mimics large Stokes shift fluorescent proteins and exhibits high affinity for 3,5-dimethoxy-4-hydroxybenzylidene imidazolone (DMHBI) derivatives to elicit green or red fluorescence emission. Here, we elucidate the structural and mechanistic basis of fluorescence activation by crystallography and time-resolved optical spectroscopy. Two co-crystal structures of the Chili RNA with positively charged DMHBO+ andFluorogenic RNA aptamers are synthetic functional RNAs that specifically bind and activate conditional fluorophores. The Chili RNA aptamer mimics large Stokes shift fluorescent proteins and exhibits high affinity for 3,5-dimethoxy-4-hydroxybenzylidene imidazolone (DMHBI) derivatives to elicit green or red fluorescence emission. Here, we elucidate the structural and mechanistic basis of fluorescence activation by crystallography and time-resolved optical spectroscopy. Two co-crystal structures of the Chili RNA with positively charged DMHBO+ and DMHBI+ ligands revealed a G-quadruplex and a trans-sugar-sugar edge G:G base pair that immobilize the ligand by π-π stacking. A Watson-Crick G:C base pair in the fluorophore binding site establishes a short hydrogen bond between the N7 of guanine and the phenolic OH of the ligand. Ultrafast excited state proton transfer (ESPT) from the neutral chromophore to the RNA was found with a time constant of 130 fs and revealed the mode of action of the large Stokes shift fluorogenic RNA aptamer.…
Author: | Mateusz Mieczkowski, Christian Steinmetzger, Irene Bessi, Ann-Kathrin Lenz, Alexander Schmiedel, Marco Holzapfel, Christoph LambertORCiD, Vladimir Pena, Claudia HöbartnerORCiD |
---|---|
URN: | urn:nbn:de:bvb:20-opus-254527 |
Document Type: | Journal article |
Faculties: | Fakultät für Chemie und Pharmazie / Institut für Organische Chemie |
Language: | English |
Parent Title (English): | Nature Communications |
Year of Completion: | 2021 |
Volume: | 12 |
Pagenumber: | 3549 |
Source: | Nature Communications 12, 3549 (2021). https://doi.org/10.1038/s41467-021-23932-0 |
DOI: | https://doi.org/10.1038/s41467-021-23932-0 |
Sonstige beteiligte Institutionen: | Georg August University School of Science |
Sonstige beteiligte Institutionen: | Max Planck Institute for Biophysical Chemistry |
Sonstige beteiligte Institutionen: | Institute of Cancer Research (ICR) London |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 547 Organische Chemie |
Tag: | Chili RNA Aptamer; Co-Crystal Structures of Chili RNA; Fluorogenic RNA Aptamers; Optical Spectroscopy; RNA; Structural Biology; Synthetic Functional RNAs; X-ray Crystallography |
Release Date: | 2022/02/02 |
EU-Project number / Contract (GA) number: | 682586 |
OpenAIRE: | OpenAIRE |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |