Combining Coarse-Grained Simulations and Single Molecule Analysis Reveals a Three-State Folding Model of the Guanidine-II Riboswitch
- Author(s)
- Christin Fuks, Sebastian Falkner, Nadine Schwierz, Martin Hengesbach
- Abstract
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 Mg
2+ 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 Mg
2+ 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.
- Organisation(s)
- Computational and Soft Matter Physics
- External organisation(s)
- Johann Wolfgang Goethe-Universität Frankfurt am Main, Max Planck Institute of Biophysics
- Journal
- Frontiers in Molecular Biosciences
- Volume
- 9
- No. of pages
- 16
- ISSN
- 2296-889X
- DOI
- https://doi.org/10.3389/fmolb.2022.826505
- Publication date
- 04-2022
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 106041 Structural biology, 103029 Statistical physics
- Keywords
- ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology (miscellaneous), Molecular Biology, Biochemistry
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/be5eb37a-1ac5-448e-9f77-d0996257fe24