Mn2+-Sensing Mechanisms of yybP-ykoY Orphan Riboswitches
Open accessAbstract
Gene regulation in cis by riboswitches is prevalent in bacteria. The yybP-ykoY riboswitch family is quite widespread, yet its ligand and function remained unknown. Here, we characterize the Lactococcus lactis yybP-ykoY orphan riboswitch as a Mn(2+)-dependent transcription-ON riboswitch, with a ∼30-40 μM affinity for Mn(2+). We further determined its crystal structure at 2.7 Å to elucidate the metal sensing mechanism. The riboswitch resembles a hairpin, with two coaxially stacked helices tethered by a four-way junction and a tertiary docking interface. The Mn(2+)-sensing region, strategically located at the highly conserved docking interface, has two metal binding sites. Whereas one site tolerates the binding of either Mg(2+) or Mn(2+), the other site strongly prefers Mn(2+) due to a direct contact from the N7 of an invariable adenosine. Mutagenesis and a Mn(2+)-free E. coli yybP-ykoY structure further reveal that Mn(2+) binding is coupled with stabilization of the Mn(2+)-sensing region and the aptamer domain.
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Best estimates of the labile manganese pool in model bacteria derive from measurements of the amount of free Mn2+ required for regulation of gene expression by Mn2+-dependent regulators such as MntR and Mn2+-dependent riboswitches.
“Our current best estimates of the labile manganese pool in model bacteria derive from measurements of the amount of free Mn2+ required for regulation of gene expression by Mn2+-dependent regulators such as the MntR transcription factor101,102 and Mn2+-dependent riboswitches.103”
From Metals in Motion: Understanding Labile Metal Pools in Bacteria (2025) · cites this paper as [103]
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Self-citation
- Authors
- Price, I. R., Gaballa, A., Ding, F., Helmann, J. D., & Ke, A.
- Affiliations
- Cornell University (US)
- Corresponding author
- Ke, Ailong
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2015-03
- Volume
- 57
- Issue
- 6
- Pages
- 1110-1123
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC4703321
- OpenAlex
- W1993159927
- Cited by
- 136
- References
- 5
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 15 · 2023: 7 · 2022: 20 · 2021: 14 · 2020: 11 · 2019: 11 · 2018: 7 · 2017: 15 · 2016: 13 · 2015: 6
- FWCI
- 5.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 384 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- Funders
- NIH (GM086766, GM102543, GM059323)
- National Center for Research Resources at the NIH (RR15301)
- U.S. Department of Energy, Office of Basic Energy Sciences (W31-109-ENG-38)
- National Science Foundation (DMR-0936384)
- NIGMS (GM103485)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Keywords
- metal ion binding, transcriptional regulation, Lactococcus lactis, crystal structure, metal binding sites, cis-regulation, Escherichia coli
- MeSH terms
- Adenosine Triphosphatases, Bacillus subtilis, Base Sequence, Escherichia coli, Magnesium, Models, Molecular, Molecular Sequence Data, Mutation, Nucleic Acid Conformation, RNA, Bacterial, Lactococcus lactis, Gene Expression Regulation, Bacterial, Mutagenesis, Site-Directed, Crystallography, X-Ray, Regulatory Sequences, Ribonucleic Acid, Quorum Sensing, Riboswitch
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