IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-40483-8.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-40483-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-40483-8?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Alexander J. Meeske & Eammon P. Riley & William P. Robins & Tsuyoshi Uehara & John J. Mekalanos & Daniel Kahne & Suzanne Walker & Andrew C. Kruse & Thomas G. Bernhardt & David Z. Rudner, 2016. "SEDS proteins are a widespread family of bacterial cell wall polymerases," Nature, Nature, vol. 537(7622), pages 634-638, September.
    2. 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.
    3. 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.
    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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. 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.
    2. Brooke M. Britton & Remy A. Yovanno & Sara F. Costa & Joshua McCausland & Albert Y. Lau & Jie Xiao & Zach Hensel, 2023. "Conformational changes in the essential E. coli septal cell wall synthesis complex suggest an activation mechanism," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Yoshikazu Kawai & Maki Kawai & Eilidh Sohini Mackenzie & Yousef Dashti & Bernhard Kepplinger & Kevin John Waldron & Jeff Errington, 2023. "On the mechanisms of lysis triggered by perturbations of bacterial cell wall biosynthesis," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    4. Huan Zhang & Srutha Venkatesan & Emily Ng & Beiyan Nan, 2023. "Coordinated peptidoglycan synthases and hydrolases stabilize the bacterial cell wall," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    5. Shailab Shrestha & Najwa Taib & Simonetta Gribaldo & Aimee Shen, 2023. "Diversification of division mechanisms in endospore-forming bacteria revealed by analyses of peptidoglycan synthesis in Clostridioides difficile," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    6. Michael D. Sacco & Shaohui Wang & Swamy R. Adapa & Xiujun Zhang & Eric M. Lewandowski & Maura V. Gongora & Dimitra Keramisanou & Zachary D. Atlas & Julia A. Townsend & Jean R. Gatdula & Ryan T. Morgan, 2022. "A unique class of Zn2+-binding serine-based PBPs underlies cephalosporin resistance and sporogenesis in Clostridioides difficile," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40483-8. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.