TY  - JOUR
A1  - Fuks, Christin
A1  - Falkner, Sebastian
A1  - Schwierz, Nadine
A1  - Hengesbach, Martin
T1  - Combining oarse-grained simulations and single molecule analysis reveals a three-state cfolding model of the guanidine-II Riboswitch
T2  - Frontiers in molecular biosciences
N2  - 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.
KW  - single-molecule FRET
KW  - coarse-grained simulations
KW  - riboswitch
KW  - guanidine-II riboswitch
KW  - RNA dynamics
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/74240
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-742403
SN  - 2296-889X
N1  - This work was supported by the DFG (CRC902 to MH and SF, Emmy Noether Programme, grant no. 315221747 to NS).
N1  - The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
VL  - 9
IS  - art. 826505
SP  - 1
EP  - 16
PB  - Frontiers
CY  - Lausanne
ER  -