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Structural basis of peptidoglycan synthesis by E. coli RodA-PBP2 complex

Author

Listed:
  • Rie Nygaard

    (Columbia University Irving Medical Center)

  • Chris L. B. Graham

    (University of Warwick)

  • Meagan Belcher Dufrisne

    (University of Virginia)

  • Jonathan D. Colburn

    (University of Warwick
    University of Warwick)

  • Joseph Pepe

    (Columbia University Irving Medical Center)

  • Molly A. Hydorn

    (Columbia University Irving Medical Center)

  • Silvia Corradi

    (Columbia University Irving Medical Center
    Sapienza University of Rome)

  • Chelsea M. Brown

    (University of Warwick
    University of Warwick)

  • Khuram U. Ashraf

    (Columbia University Irving Medical Center)

  • Owen N. Vickery

    (University of Warwick
    University of Warwick)

  • Nicholas S. Briggs

    (University of Warwick)

  • John J. Deering

    (University of Warwick)

  • Brian Kloss

    (New York Structural Biology Center)

  • Bruno Botta

    (Sapienza University of Rome)

  • Oliver B. Clarke

    (Columbia University Irving Medical Center
    Columbia University Irving Medical Center)

  • Linda Columbus

    (University of Virginia)

  • Jonathan Dworkin

    (Columbia University Irving Medical Center)

  • Phillip J. Stansfeld

    (University of Warwick
    University of Warwick)

  • David I. Roper

    (University of Warwick)

  • Filippo Mancia

    (Columbia University Irving Medical Center)

Abstract

Peptidoglycan (PG) is an essential structural component of the bacterial cell wall that is synthetized during cell division and elongation. PG forms an extracellular polymer crucial for cellular viability, the synthesis of which is the target of many antibiotics. PG assembly requires a glycosyltransferase (GT) to generate a glycan polymer using a Lipid II substrate, which is then crosslinked to the existing PG via a transpeptidase (TP) reaction. A Shape, Elongation, Division and Sporulation (SEDS) GT enzyme and a Class B Penicillin Binding Protein (PBP) form the core of the multi-protein complex required for PG assembly. Here we used single particle cryo-electron microscopy to determine the structure of a cell elongation-specific E. coli RodA-PBP2 complex. We combine this information with biochemical, genetic, spectroscopic, and computational analyses to identify the Lipid II binding sites and propose a mechanism for Lipid II polymerization. Our data suggest a hypothesis for the movement of the glycan strand from the Lipid II polymerization site of RodA towards the TP site of PBP2, functionally linking these two central enzymatic activities required for cell wall peptidoglycan biosynthesis.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40483-8
    DOI: 10.1038/s41467-023-40483-8
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    References listed on IDEAS

    as
    1. Alexandre Martins & Carlos Contreras-Martel & Manon Janet-Maitre & Mayara M. Miyachiro & Leandro F. Estrozi & Daniel Maragno Trindade & Caíque C. Malospirito & Fernanda Rodrigues-Costa & Lionel Imbert, 2021. "Self-association of MreC as a regulatory signal in bacterial cell wall elongation," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
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    3. Irina Shlosman & Elayne M. Fivenson & Morgan S. A. Gilman & Tyler A. Sisley & Suzanne Walker & Thomas G. Bernhardt & Andrew C. Kruse & Joseph J. Loparo, 2023. "Allosteric activation of cell wall synthesis during bacterial growth," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. 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.
    5. Megan Sjodt & Kelly Brock & Genevieve Dobihal & Patricia D. A. Rohs & Anna G. Green & Thomas A. Hopf & Alexander J. Meeske & Veerasak Srisuknimit & Daniel Kahne & Suzanne Walker & Debora S. Marks & Th, 2018. "Structure of the peptidoglycan polymerase RodA resolved by evolutionary coupling analysis," Nature, Nature, vol. 556(7699), pages 118-121, April.
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