IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-29836-x.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-29836-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-29836-x?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. 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.
    2. 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.
    3. 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.
    4. 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.
    5. 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.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    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.

    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. Takeshi Nakaya & Miyuki Yabe & Ellene H. Mashalidis & Toyotaka Sato & Kazuki Yamamoto & Yuta Hikiji & Akira Katsuyama & Motoko Shinohara & Yusuke Minato & Satoshi Takahashi & Motohiro Horiuchi & Shin-, 2022. "Synthesis of macrocyclic nucleoside antibacterials and their interactions with MraY," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Jixing Lyu & Chang Liu & Tianqi Zhang & Samantha Schrecke & Nicklaus P. Elam & Charles Packianathan & Georg K. A. Hochberg & David Russell & Minglei Zhao & Arthur Laganowsky, 2022. "Structural basis for lipid and copper regulation of the ABC transporter MsbA," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    3. Xiaoyu Zhou & Zhuofan Wang & Jingjin Fan & Zheng Ouyang, 2023. "High-resolution separation of bioisomers using ion cloud profiling," Nature Communications, Nature, vol. 14(1), pages 1-6, December.
    4. Vishal Maingi & Zhao Zhang & Chris Thachuk & Namita Sarraf & Edwin R. Chapman & Paul W. K. Rothemund, 2023. "Digital nanoreactors to control absolute stoichiometry and spatiotemporal behavior of DNA receptors within lipid bilayers," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    5. Miaoqi Chu & Zhang Jiang & Michael Wojcik & Tao Sun & Michael Sprung & Jin Wang, 2023. "Probing three-dimensional mesoscopic interfacial structures in a single view using multibeam X-ray coherent surface scattering and holography imaging," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    6. Yun Zhu & Bo-Ji Peng & Smriti Kumar & Lauren Stover & Jing-Yuan Chang & Jixing Lyu & Tianqi Zhang & Samantha Schrecke & Djavdat Azizov & David H. Russell & Lei Fang & Arthur Laganowsky, 2023. "Polyamine detergents tailored for native mass spectrometry studies of membrane proteins," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    7. Yongchan Lee & Pattama Wiriyasermkul & Pornparn Kongpracha & Satomi Moriyama & Deryck J. Mills & Werner Kühlbrandt & Shushi Nagamori, 2022. "Ca2+-mediated higher-order assembly of heterodimers in amino acid transport system b0,+ biogenesis and cystinuria," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    8. Junke Liu & Hengmin Tang & Chanjuan Xu & Shengnan Zhou & Xunying Zhu & Yuanyuan Li & Laurent Prézeau & Tao Xu & Jean-Philippe Pin & Philippe Rondard & Wei Ji & Jianfeng Liu, 2022. "Biased signaling due to oligomerization of the G protein-coupled platelet-activating factor receptor," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    9. Ondřej Gahura & Alexander Mühleip & Carolina Hierro-Yap & Brian Panicucci & Minal Jain & David Hollaus & Martina Slapničková & Alena Zíková & Alexey Amunts, 2022. "An ancestral interaction module promotes oligomerization in divergent mitochondrial ATP synthases," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    10. Iven Winkelmann & Povilas Uzdavinys & Ian M. Kenney & Joseph Brock & Pascal F. Meier & Lina-Marie Wagner & Florian Gabriel & Sukkyeong Jung & Rei Matsuoka & Christoph Ballmoos & Oliver Beckstein & Dav, 2022. "Crystal structure of the Na+/H+ antiporter NhaA at active pH reveals the mechanistic basis for pH sensing," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    11. Atsushi Yamagata & Yoshiko Murata & Kosuke Namba & Tohru Terada & Shuya Fukai & Mikako Shirouzu, 2022. "Uptake mechanism of iron-phytosiderophore from the soil based on the structure of yellow stripe transporter," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    12. Jianqiang Mu & Chenyang Xue & Lei Fu & Zongjun Yu & Minhan Nie & Mengqi Wu & Xinmeng Chen & Kun Liu & Ruiqian Bu & Ying Huang & Baisheng Yang & Jianming Han & Qianru Jiang & Kevin C. Chan & Ruhong Zho, 2023. "Conformational cycle of human polyamine transporter ATP13A2," Nature Communications, Nature, vol. 14(1), pages 1-12, 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:13:y:2022:i:1:d:10.1038_s41467-022-29836-x. 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.