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Molecular dissection of the glutamine synthetase-GlnR nitrogen regulatory circuitry in Gram-positive bacteria

Author

Listed:
  • Brady A. Travis

    (Duke University Medical Center)

  • Jared V. Peck

    (University of North Carolina)

  • Raul Salinas

    (Duke University Medical Center)

  • Brandon Dopkins

    (Duke University Medical Center)

  • Nicholas Lent

    (Duke University Medical Center)

  • Viet D. Nguyen

    (Duke University Medical Center)

  • Mario J. Borgnia

    (Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services)

  • Richard G. Brennan

    (Duke University Medical Center)

  • Maria A. Schumacher

    (Duke University Medical Center)

Abstract

How bacteria sense and respond to nitrogen levels are central questions in microbial physiology. In Gram-positive bacteria, nitrogen homeostasis is controlled by an operon encoding glutamine synthetase (GS), a dodecameric machine that assimilates ammonium into glutamine, and the GlnR repressor. GlnR detects nitrogen excess indirectly by binding glutamine-feedback-inhibited-GS (FBI-GS), which activates its transcription-repression function. The molecular mechanisms behind this regulatory circuitry, however, are unknown. Here we describe biochemical and structural analyses of GS and FBI-GS-GlnR complexes from pathogenic and non-pathogenic Gram-positive bacteria. The structures show FBI-GS binds the GlnR C-terminal domain within its active-site cavity, juxtaposing two GlnR monomers to form a DNA-binding-competent GlnR dimer. The FBI-GS-GlnR interaction stabilizes the inactive GS conformation. Strikingly, this interaction also favors a remarkable dodecamer to tetradecamer transition in some GS, breaking the paradigm that all bacterial GS are dodecamers. These data thus unveil unique structural mechanisms of transcription and enzymatic regulation.

Suggested Citation

  • Brady A. Travis & Jared V. Peck & Raul Salinas & Brandon Dopkins & Nicholas Lent & Viet D. Nguyen & Mario J. Borgnia & Richard G. Brennan & Maria A. Schumacher, 2022. "Molecular dissection of the glutamine synthetase-GlnR nitrogen regulatory circuitry in Gram-positive bacteria," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31573-0
    DOI: 10.1038/s41467-022-31573-0
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    References listed on IDEAS

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    1. Ekaterina E. Zheleznova Heldwein & Richard G. Brennan, 2001. "Crystal structure of the transcription activator BmrR bound to DNA and a drug," Nature, Nature, vol. 409(6818), pages 378-382, January.
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    Cited by:

    1. Marcus Ziemann & Viktoria Reimann & Yajing Liang & Yue Shi & Honglei Ma & Yuman Xie & Hui Li & Tao Zhu & Xuefeng Lu & Wolfgang R. Hess, 2023. "CvkR is a MerR-type transcriptional repressor of class 2 type V-K CRISPR-associated transposase systems," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Maria A. Schumacher & Raul Salinas & Brady A. Travis & Rajiv Ranjan Singh & Nicholas Lent, 2023. "M. mazei glutamine synthetase and glutamine synthetase-GlnK1 structures reveal enzyme regulation by oligomer modulation," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

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    1. Marcus Ziemann & Viktoria Reimann & Yajing Liang & Yue Shi & Honglei Ma & Yuman Xie & Hui Li & Tao Zhu & Xuefeng Lu & Wolfgang R. Hess, 2023. "CvkR is a MerR-type transcriptional repressor of class 2 type V-K CRISPR-associated transposase systems," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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