TY - JOUR T1 - Local-to-global signal transduction at the core of the Mn<sup>2+</sup> sensing riboswitch JF - bioRxiv DO - 10.1101/553354 SP - 553354 AU - Krishna C Suddala AU - Ian R Price AU - Michal Janeček AU - Petra Kührová AU - Shiba Dandpat AU - Jiří Šponer AU - Pavel Banáš AU - Ailong Ke AU - Nils G Walter Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/02/18/553354.abstract N2 - The widespread manganese-ion sensing yybP-ykoY riboswitch controls the expression of bacterial Mn2+ homeostasis genes. Here, we first determine the crystal structure of the ligand-bound yybP-ykoY riboswitch from Xanthomonas oryzae at 2.85 Å resolution, revealing two conformations with docked four-way junction (4WJ) and incompletely coordinated metal ions. In &gt;50 μs of MD simulations, we observe that loss of divalents from the core triggers local structural perturbations in the adjacent docking interface, laying the foundation for signal transduction to the regulatory switch helix. Using single-molecule FRET, we unveil a previously unobserved extended 4WJ conformation that samples transient docked states in the presence of Mg2+. Only upon adding sub-millimolar Mn2+, however, can the 4WJ dock stably, a feature lost upon mutation of an adenosine contacting Mn2+ in the core. These observations illuminate how subtly differing ligand preferences of competing metal ions become amplified by the coupling of local with global RNA dynamics. ER -