Local-to-global signal transduction at the core of a Mn2+ sensing riboswitch

0511789 - BFÚ 2020 RIV GB eng J - Journal Article
Suddala, K.C. - Price, I.R. - Dandpat, S.S. - Janeček, Michal - Kührová, P. - Šponer, Jiří - Banáš, Pavel - Ke, A. - Walter, N.G.
Local-to-global signal transduction at the core of a Mn2+ sensing riboswitch.
Nature Communications. Roč. 10, SEP 20 2019 (2019), č. článku 4304. E-ISSN 2041-1723
R&D Projects: GA MŠMT EF15_003/0000477
Institutional support: RVO:68081707
Keywords : molecular-dynamics * eubacteria sense * rna structure * single
OECD category: Biology (theoretical, mathematical, thermal, cryobiology, biological rhythm), Evolutionary biology
Impact factor: 12.121, year: 2019
Method of publishing: Open access
https://www.nature.com/articles/s41467-019-12230-5.pdf

The widespread Mn2+-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 aptamer from Xanthomonas oryzae at 2.96 angstrom resolution, revealing two conformations with docked four-way junction (4WJ) and incompletely coordinated metal ions. In >100 mu s 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.
Permanent Link: http://hdl.handle.net/11104/0302037