Combining Coarse-Grained Simulations and Single Molecule Analysis Reveals a Three-State Folding Model of the Guanidine-II Riboswitch

Autor(en)

Christin Fuks, Sebastian Falkner, Nadine Schwierz, Martin Hengesbach

Abstrakt

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(en)

Computergestützte Physik und Physik der Weichen Materie

Externe Organisation(en)

Johann Wolfgang Goethe-Universität Frankfurt am Main, Max-Planck-Institut für Biophysik

Journal

Frontiers in Molecular Biosciences

Band

9

Anzahl der Seiten

16

ISSN

2296-889X

DOI

https://doi.org/10.3389/fmolb.2022.826505

Publikationsdatum

04-2022

Peer-reviewed

Ja

ÖFOS 2012

106041 Strukturbiologie, 103029 Statistische Physik

Schlagwörter

ASJC Scopus Sachgebiete

Biochemistry, Genetics and Molecular Biology (miscellaneous), Molecular Biology, Biochemistry

Link zum Portal

https://ucrisportal.univie.ac.at/de/publications/be5eb37a-1ac5-448e-9f77-d0996257fe24