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Peptidoglycan biosynthesis is driven by lipid transfer along enzyme-substrate affinity gradients

Author

Listed:
  • Abraham O. Oluwole

    (University of Oxford
    The Kavli Institute for Nanoscience Discovery)

  • Robin A. Corey

    (University of Oxford)

  • Chelsea M. Brown

    (University of Warwick)

  • Victor M. Hernández-Rocamora

    (Newcastle University)

  • Phillip J. Stansfeld

    (University of Oxford
    University of Warwick)

  • Waldemar Vollmer

    (Newcastle University)

  • Jani R. Bolla

    (The Kavli Institute for Nanoscience Discovery
    University of Oxford)

  • Carol V. Robinson

    (University of Oxford
    The Kavli Institute for Nanoscience Discovery)

Abstract

Maintenance of bacterial cell shape and resistance to osmotic stress by the peptidoglycan (PG) renders PG biosynthetic enzymes and precursors attractive targets for combating bacterial infections. Here, by applying native mass spectrometry, we elucidate the effects of lipid substrates on the PG membrane enzymes MraY, MurG, and MurJ. We show that dimerization of MraY is coupled with binding of the carrier lipid substrate undecaprenyl phosphate (C55-P). Further, we demonstrate the use of native MS for biosynthetic reaction monitoring and find that the passage of substrates and products is controlled by the relative binding affinities of the different membrane enzymes. Overall, we provide a molecular view of how PG membrane enzymes convey lipid precursors through favourable binding events and highlight possible opportunities for intervention.

Suggested Citation

  • Abraham O. Oluwole & Robin A. Corey & Chelsea M. Brown & Victor M. Hernández-Rocamora & Phillip J. Stansfeld & Waldemar Vollmer & Jani R. Bolla & Carol V. Robinson, 2022. "Peptidoglycan biosynthesis is driven by lipid transfer along enzyme-substrate affinity gradients," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29836-x
    DOI: 10.1038/s41467-022-29836-x
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    References listed on IDEAS

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    1. Kallol Gupta & Joseph A. C. Donlan & Jonathan T. S. Hopper & Povilas Uzdavinys & Michael Landreh & Weston B. Struwe & David Drew & Andrew J. Baldwin & Phillip J. Stansfeld & Carol V. Robinson, 2017. "The role of interfacial lipids in stabilizing membrane protein oligomers," Nature, Nature, vol. 541(7637), pages 421-424, January.
    2. Hannah Piepenbreier & Angelika Diehl & Georg Fritz, 2019. "Minimal exposure of lipid II cycle intermediates triggers cell wall antibiotic resistance," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    3. Ben C. Chung & Ellene H. Mashalidis & Tetsuya Tanino & Mijung Kim & Akira Matsuda & Jiyong Hong & Satoshi Ichikawa & Seok-Yong Lee, 2016. "Structural insights into inhibition of lipid I production in bacterial cell wall synthesis," Nature, Nature, vol. 533(7604), pages 557-560, May.
    4. Ellene H. Mashalidis & Benjamin Kaeser & Yuma Terasawa & Akira Katsuyama & Do-Yeon Kwon & Kiyoun Lee & Jiyong Hong & Satoshi Ichikawa & Seok-Yong Lee, 2019. "Chemical logic of MraY inhibition by antibacterial nucleoside natural products," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    5. Arthur Laganowsky & Eamonn Reading & Timothy M. Allison & Martin B. Ulmschneider & Matteo T. Degiacomi & Andrew J. Baldwin & Carol V. Robinson, 2014. "Membrane proteins bind lipids selectively to modulate their structure and function," Nature, Nature, vol. 510(7503), pages 172-175, June.
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    Cited by:

    1. Rie Nygaard & Chris L. B. Graham & Meagan Belcher Dufrisne & Jonathan D. Colburn & Joseph Pepe & Molly A. Hydorn & Silvia Corradi & Chelsea M. Brown & Khuram U. Ashraf & Owen N. Vickery & Nicholas S. , 2023. "Structural basis of peptidoglycan synthesis by E. coli RodA-PBP2 complex," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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