Local-to-global signal transduction at the core of a Mn2+ sensing riboswitch
| Autor: | Ian R. Price, Krishna C. Suddala, Pavel Banáš, Shiba S. Dandpat, Nils G. Walter, Jiří Šponer, Ailong Ke, Petra Kührová, Michal Janeček |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Riboswitch Aptamer Science General Physics and Astronomy 01 natural sciences General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Xanthomonas oryzae 0103 physical sciences Binding site lcsh:Science Multidisciplinary 010304 chemical physics biology Chemistry RNA General Chemistry biology.organism_classification 030104 developmental biology Förster resonance energy transfer Docking (molecular) Biophysics lcsh:Q Signal transduction |
| Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-16 (2019) |
| ISSN: | 2041-1723 |
| Popis: | 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 A resolution, revealing two conformations with docked four-way junction (4WJ) and incompletely coordinated metal ions. In >100 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. Riboswitches bind intracellular metabolites and control bacterial gene expression. Here, by using X-ray crystallography, molecular dynamics simulations, and single-molecule fluorescence resonance energy transfer, the authors show how a local Mn2+ ion-binding signal is transduced across the yybP-ykoY riboswitch from Xanthomonas oryzae. |
| Databáze: | OpenAIRE |
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