Tiny but multi-stable: four distinct conformational states govern the ligand-free state of the preQ1 riboswitch from a thermophilic bacterium
Year: 2025
Type: article
Abstract: Translational riboswitches are bacterial gene regulatory elements located in the 5'-untranslated region of mRNAs. They operate through a conformational refolding reaction that is triggered by a change in concentration of a modulating small molecule ligand. The initially model posited that the two functional states, the ligand-bound and ligand-free state, would only populate two stable conformations. However, the subsequent discoveries of multiple conformations for the apo- and holo-states of riboswitches have rendered this model obsolete. Concomitantly, a comprehensive account of the conformational multistability of riboswitches has remained elusive. In this study, we demonstrate that even the smallest naturally occurring translational riboswitch, the preQ1-sensing riboswitch from Thermoanaerobacter tengcongensis, adopts four distinct and structurally different conformations in the absence of ligand. This is in contrast to structures determined by X-ray crystallography, which reveal only minor deviations between the ligand-free and ligand-bound states. Utilizing NMR-spectroscopic analysis, we characterize the structurally heterogeneous apo-state and depict four distinct conformations that demonstrate varying temperature stabilities. Upon ligand-binding, the folding pathway undergoes kinetic partitioning, thereby enabling regulatory plasticity to integrate multiple environmental inputs for riboswitch-based gene regulation.
Source: Nucleic Acids Research
DOI: 10.1093/nar/gkaf560
Authors: Stefanie Rückriegel, Konstantinos Stamatakis, Josef Wachtveitl, Boris Fürtig
Institution: Goethe University Frankfurt
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,992
OpenAlex ID: W4411782605