4.8 Article

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

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NATURE COMMUNICATIONS
卷 10, 期 -, 页码 -

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NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-12230-5

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资金

  1. NIH [GM062357, GM118524, GM118174]
  2. project SYMBIT - ERDF [CZ. 02.1.01/0.0/0.0/15_003/0000477]
  3. Grant Agency of the Czech Republic [18-25349S]
  4. Palacky University Olomouc [IGA_PrF_2019_031]
  5. National Institute of General Medical Sciences from the National Institutes of Health [P30 GM124165]
  6. NIH-ORIP HEI grant [S10 RR029205]
  7. DOE Office of Science [DE-AC02-06CH11357]

向作者/读者索取更多资源

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.

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