Manganese

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Rfam ID: RF00080 (yybP-ykoY manganese riboswitch)


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Timeline Description Structure&recognition References


Timeline

Start

    2004[1] Discovery of yybP-ykoY motif

    Identify the yybP-ykoY motif as a manganese ion sensor 2015[2]

    2015[3] Mn2+-sensing mechanisms of yybP-ykoY riboswitches

    Demonstrating how the broad family of yybP-ykoY riboswitches use heptacoordination to selectively bind transition metal ions 2018[4]

    2019[5] The S.pneumoniae yybP-ykoY riboswitch functions to regulate Ca2+ efflux

    The ligand-dependent (un)folding path-way of the Mn2+ sensing riboswitch 2019[6]
2023...



Description

 The yybP-ykoY leader RNA element was originally discovered in E. coli during a large scale screen and was named SraF. This family was later found to exist upstream of related families of protein genes in many bacteria, including the yybP and ykoY genes in B. subtilis. The specific functions of these proteins are unknown, but this structured RNA element may be involved in their genetic regulation as a riboswitch. The yybP-ykoY element was later proposed to be manganese-responsive after another associated family of genes, YebN/MntP, was shown to encode Mn2+ efflux pumps in several bacteria. Genetic data and a crystal structure confirmed that yybP-ykoY is a manganese riboswitch that directly binds Mn2+ (From Wikipedia).


Gene association

Network of genes immediately downstream of the yybP-ykoY riboswitch are predicted to have roles in protecting against metal toxicity. P-ZnR denotes proteins with a peptidase-associated zinc-ribbon and MetJ-Arc denotes proteins with MetJ-Arc DNA-binding domains[2].
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Gene regulation

Potential mechanism of transcriptional regulation by the yybP-ykoY manganese riboswitch in Lactococcus lactis. RNA polymerase produced predominantly terminated transcripts in the absence of Mn2+. Addition of 0.5 millimolar (mM) Mn2+, but not other metals tested (Fe2+, Co2+, Ni2+,and Ca2+), led to highly efficient anti-termination. We present the prototypical mechanism, but not all possible mechanisms[3].
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Structure and Ligand recognition

2D representation

Top: Consensus sequence and secondary structure model for the yybP-ykoY manganese riboswitch. Bottom: Secondary structure depictions of the Lactococcus lactis yybP-ykoY manganese riboswitch according to PDB ID: 4Y1I[3].

5'AAAGGGGAGUAGCGUCGGGAAACCGAAACAAAGUCGUCAAUUCGUGAGGAAACUCACCGGCUUUGUUGACAUACGAAAGUAUGUUUAGCAAGACCUUUCC3' (Sequence from bottom structure )


3D visualisation

The overall structure of the Lactococcus lactis yybP-ykoY manganese riboswitch was generated from PDB ID: 4Y1I at 2.85 Å resolution. The structure shows two series of coaxially stacked helices forming an overall hairpin shape, with the highly conserved L1 (yellow) and L3 (orange) docking together and binding two metal ions. Additional available structures that have been solved and detailed information are accessible on Structures page [3].

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Binding pocket

Left: Surface representation of the binding pocket of the Lactococcus lactis yybP-ykoY manganese riboswitch generated from PDB ID: 4Y1I at 2.85 Å resolution. The manganese ion is labeled in red. Right: The metal coordination scheme. Mg2+ is coordinated octahedrally by five backbone phosphates and a water. The Mn2+ contains five backbone phosphates and the N7 of A41. N6 of A41 also makes a H-bond to the phosphate of U39[3].
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Ligand recognition

The Lactococcus lactis yybP-ykoY riboswitch binds Mn2+ with an effective Kd of ~ 30–40 micromolar (μM), as monitored by both in vitro transcription (IVT) assays and selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE). Refer to the corresponding references for comprehensive details regarding reaction conditions and species information in measuring the dissociation constant displayed below[3].
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References

[1] New RNA motifs suggest an expanded scope for riboswitches in bacterial genetic control.
Barrick, J. E. et al.
Proc. Natl. Acad. Sci. U. S. A. 101, 6421–6426 (2004).

[2] The ubiquitous yybP-ykoY riboswitch is a manganese-responsive regulatory element.
Dambach, M. et al.
Mol. Cell 57, 1099–1109 (2015).

[3] Mn(2+)-sensing mechanisms of yybP-ykoY orphan riboswitches.
Price, I. R., Gaballa, A., Ding, F., Helmann, J. D. & Ke, A.
Mol. Cell 57, 1110–1123 (2015).

[4] Convergent Use of Heptacoordination for Cation Selectivity by RNA and Protein Metalloregulators.
Bachas, S. T. & Ferré-D’Amaré, A. R.
Cell Chem Biol 25, 962–973.e5 (2018).

[5] A Mn-sensing riboswitch activates expression of a Mn2+/Ca2+ ATPase transporter in Streptococcus.
Martin, J. E. et al.
Nucleic Acids Res. 47, 6885–6899 (2019).

[6] Local-to-global signal transduction at the core of a Mn sensing riboswitch.
Suddala, K. C. et al.
Nat. Commun. 10, 4304 (2019).