Combining oarse-grained simulations and single molecule analysis reveals a three-state cfolding model of the guanidine-II Riboswitch
- Riboswitch RNAs regulate gene expression by conformational changes induced by environmental conditions and specific ligand binding. The guanidine-II riboswitch is proposed to bind the small molecule guanidinium and to subsequently form a kissing loop interaction between the P1 and P2 hairpins. While an interaction was shown for isolated hairpins in crystallization and electron paramagnetic resonance experiments, an intrastrand kissing loop formation has not been demonstrated. Here, we report the first evidence of this interaction in cis in a ligand and Mg2+ dependent manner. Using single-molecule FRET spectroscopy and detailed structural information from coarse-grained simulations, we observe and characterize three interconvertible states representing an open and kissing loop conformation as well as a novel Mg2+ dependent state for the guanidine-II riboswitch from E. coli. The results further substantiate the proposed switching mechanism and provide detailed insight into the regulation mechanism for the guanidine-II riboswitch class. Combining single molecule experiments and coarse-grained simulations therefore provides a promising perspective in resolving the conformational changes induced by environmental conditions and to yield molecular insights into RNA regulation.
Verfasserangaben: | Christin FuksGND, Sebastian FalknerORCiD, Nadine SchwierzORCiDGND, Martin HengesbachORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-742403 |
DOI: | https://doi.org/10.3389/fmolb.2022.826505 |
ISSN: | 2296-889X |
Titel des übergeordneten Werkes (Englisch): | Frontiers in molecular biosciences |
Verlag: | Frontiers |
Verlagsort: | Lausanne |
Dokumentart: | Wissenschaftlicher Artikel |
Sprache: | Englisch |
Datum der Veröffentlichung (online): | 19.04.2022 |
Datum der Erstveröffentlichung: | 19.04.2022 |
Veröffentlichende Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Datum der Freischaltung: | 21.06.2023 |
Freies Schlagwort / Tag: | RNA dynamics; coarse-grained simulations; guanidine-II riboswitch; riboswitch; single-molecule FRET |
Jahrgang: | 9 |
Ausgabe / Heft: | art. 826505 |
Aufsatznummer: | 826505 |
Seitenzahl: | 16 |
Erste Seite: | 1 |
Letzte Seite: | 16 |
Bemerkung: | This work was supported by the DFG (CRC902 to MH and SF, Emmy Noether Programme, grant no. 315221747 to NS). |
Bemerkung: | The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. |
HeBIS-PPN: | 510033032 |
Institute: | Biochemie, Chemie und Pharmazie |
Angeschlossene und kooperierende Institutionen / MPI für Biophysik | |
DDC-Klassifikation: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie | |
Sammlungen: | Universitätspublikationen |
Lizenz (Deutsch): | Creative Commons - CC BY - Namensnennung 4.0 International |