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Allosteric activation of cell wall synthesis during bacterial growth

Author

Listed:
  • Irina Shlosman

    (Harvard Medical School)

  • Elayne M. Fivenson

    (Harvard Medical School)

  • Morgan S. A. Gilman

    (Harvard Medical School)

  • Tyler A. Sisley

    (Harvard Medical School)

  • Suzanne Walker

    (Harvard Medical School)

  • Thomas G. Bernhardt

    (Harvard Medical School
    Harvard Medical School)

  • Andrew C. Kruse

    (Harvard Medical School)

  • Joseph J. Loparo

    (Harvard Medical School)

Abstract

The peptidoglycan (PG) cell wall protects bacteria against osmotic lysis and determines cell shape, making this structure a key antibiotic target. Peptidoglycan is a polymer of glycan chains connected by peptide crosslinks, and its synthesis requires precise spatiotemporal coordination between glycan polymerization and crosslinking. However, the molecular mechanism by which these reactions are initiated and coupled is unclear. Here we use single-molecule FRET and cryo-EM to show that an essential PG synthase (RodA-PBP2) responsible for bacterial elongation undergoes dynamic exchange between closed and open states. Structural opening couples the activation of polymerization and crosslinking and is essential in vivo. Given the high conservation of this family of synthases, the opening motion that we uncovered likely represents a conserved regulatory mechanism that controls the activation of PG synthesis during other cellular processes, including cell division.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39037-9
    DOI: 10.1038/s41467-023-39037-9
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    References listed on IDEAS

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    1. Carlos Contreras-Martel & Alexandre Martins & Chantal Ecobichon & Daniel Maragno Trindade & Pierre-Jean Matteï & Samia Hicham & Pierre Hardouin & Meriem El Ghachi & Ivo G. Boneca & Andréa Dessen, 2017. "Molecular architecture of the PBP2–MreC core bacterial cell wall synthesis complex," Nature Communications, Nature, vol. 8(1), pages 1-10, December.
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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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