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

Suddala, Krishna C.; Price, Ian R.; Dandpat, Shiba S.; Janeček, Michal; Kührová, Petra; Šponer, Jiří; Banáš, Pavel; Ke, Ailong; Walter, Nils G.

doi:10.1038/s41467-019-12230-5

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

Journal Article · Fri Sep 20 00:00:00 EDT 2019 · Nature Communications

DOI:https://doi.org/10.1038/s41467-019-12230-5· OSTI ID:1574155

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^[2]; Dandpat, Shiba S. ^[1];

^[3]; Kührová, Petra ^[4];

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Univ. of Michigan, Ann Arbor, MI (United States)
Cornell Univ., Ithaca, NY (United States)
Czech Academy of Sciences (CAS), Brno (Czech Republic). Institute of Biophysics; Palacky University, Olomouc (Czech Republic)
Palacky University, Olomouc (Czech Republic)

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 Å 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.

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Research Organization:: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE Office of Science (SC); National Institutes of Health (NIH); Grant Agency of the Czech Republic

Grant/Contract Number:: AC02-06CH11357; GM062357; GM118524; GM118174; 18-25349S; P30 GM124165; S10 RR029205

OSTI ID:: 1574155

Journal Information:: Nature Communications, Vol. 10, Issue 1; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 13 works

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