Mn2+-Sensing Mechanisms of yybP-ykoY Orphan Riboswitches

Price, Ian R.; Gaballa, Ahmed; Ding, Fang; Helmann, John D.; Ke, Ailong

doi:10.1016/j.molcel.2015.02.016

Title: Mn2+-Sensing Mechanisms of yybP-ykoY Orphan Riboswitches

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Abstract

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 in this paper, we characterize the Lactococcus lactis yybP-ykoY orphan riboswitch as a Mn2+-dependent transcription-ON riboswitch, with a ~30–40 μM affinity for Mn²⁺. 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 Mn²⁺-sensing region, strategically located at the highly conserved docking interface, has two metal binding sites. Whereas one site tolerates the binding of either Mg²⁺ or Mn²⁺, the other site strongly prefers Mn²⁺ due to a direct contact from the N7 of an invariable adenosine. Lastly, mutagenesis and a Mn²⁺-free E. coli yybP-ykoY structure further reveal that Mn²⁺ binding is coupled with stabilization of the Mn2+-sensing region and the aptamer domain.

Authors:: Price, Ian R.; Gaballa, Ahmed; Ding, Fang; Helmann, John D.; Ke, Ailong

Publication Date:: Sun Mar 01 00:00:00 EST 2015

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

Sponsoring Org.:: USDOE Office of Science (SC), Basic Energy Sciences (BES)

OSTI Identifier:: 1242552

Alternate Identifier(s):: OSTI ID: 1177428; OSTI ID: 1233999

Grant/Contract Number:: W31-109-ENG-38; GM086766; GM102543; GM059323; RR15301; GM103485; DMR-0936384

Resource Type:: Published Article

Journal Name:: Molecular Cell

Additional Journal Information:: Journal Name: Molecular Cell Journal Volume: 57 Journal Issue: 6; Journal ID: ISSN 1097-2765

Publisher:: Elsevier

Country of Publication:: United States

Language:: English

Subject:: 59 BASIC BIOLOGICAL SCIENCES

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                    Price, Ian R., Gaballa, Ahmed, Ding, Fang, Helmann, John D., and Ke, Ailong. Mn2+-Sensing Mechanisms of yybP-ykoY Orphan Riboswitches.  United States: N. p., 2015. 
Web.  doi:10.1016/j.molcel.2015.02.016.

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                    Price, Ian R., Gaballa, Ahmed, Ding, Fang, Helmann, John D., & Ke, Ailong. Mn2+-Sensing Mechanisms of yybP-ykoY Orphan Riboswitches.  United States.  https://doi.org/10.1016/j.molcel.2015.02.016

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                    Price, Ian R., Gaballa, Ahmed, Ding, Fang, Helmann, John D., and Ke, Ailong. Sun .  
"Mn2+-Sensing Mechanisms of yybP-ykoY Orphan Riboswitches".  United States.  https://doi.org/10.1016/j.molcel.2015.02.016.

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@article{osti_1242552,

  title        = {Mn2+-Sensing Mechanisms of yybP-ykoY Orphan Riboswitches},

  author       = {Price, Ian R. and Gaballa, Ahmed and Ding, Fang and Helmann, John D. and Ke, Ailong},

  abstractNote = {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 in this paper, we characterize the Lactococcus lactis yybP-ykoY orphan riboswitch as a Mn2+-dependent transcription-ON riboswitch, with a ~30–40 μM affinity for Mn2+. 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 Mn2+-sensing region, strategically located at the highly conserved docking interface, has two metal binding sites. Whereas one site tolerates the binding of either Mg2+ or Mn2+, the other site strongly prefers Mn2+ due to a direct contact from the N7 of an invariable adenosine. Lastly, mutagenesis and a Mn2+-free E. coli yybP-ykoY structure further reveal that Mn2+ binding is coupled with stabilization of the Mn2+-sensing region and the aptamer domain.},

  doi          = {10.1016/j.molcel.2015.02.016},

  journal      = {Molecular Cell},

  number       = 6,

  volume       = 57,

  place        = {United States},

  year         = {Sun Mar 01 00:00:00 EST 2015},

  month        = {Sun Mar 01 00:00:00 EST 2015}

}

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