IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-30373-w.html
   My bibliography  Save this article

Substrate recognition and cryo-EM structure of the ribosome-bound TAC toxin of Mycobacterium tuberculosis

Author

Listed:
  • Moise Mansour

    (Université de Toulouse, CNRS, UPS)

  • Emmanuel Giudice

    (Institut de Génétique et Développement de Rennes (IGDR), UMR6290, Université de Rennes, CNRS)

  • Xibing Xu

    (Université de Toulouse, CNRS, UPS)

  • Hatice Akarsu

    (University of Fribourg & Swiss Institute of Bioinformatics
    University of Bern)

  • Patricia Bordes

    (Université de Toulouse, CNRS, UPS)

  • Valérie Guillet

    (Université de Toulouse, CNRS, UPS)

  • Donna-Joe Bigot

    (Université de Toulouse, CNRS, UPS
    Université de Toulouse, CNRS, UPS)

  • Nawel Slama

    (Université de Toulouse, CNRS, UPS)

  • Gaetano D’urso

    (Institut de Génétique et Développement de Rennes (IGDR), UMR6290, Université de Rennes, CNRS)

  • Sophie Chat

    (Institut de Génétique et Développement de Rennes (IGDR), UMR6290, Université de Rennes, CNRS)

  • Peter Redder

    (Université de Toulouse, CNRS, UPS)

  • Laurent Falquet

    (University of Fribourg & Swiss Institute of Bioinformatics)

  • Lionel Mourey

    (Université de Toulouse, CNRS, UPS)

  • Reynald Gillet

    (Institut de Génétique et Développement de Rennes (IGDR), UMR6290, Université de Rennes, CNRS)

  • Pierre Genevaux

    (Université de Toulouse, CNRS, UPS)

Abstract

Toxins of toxin-antitoxin systems use diverse mechanisms to control bacterial growth. Here, we focus on the deleterious toxin of the atypical tripartite toxin-antitoxin-chaperone (TAC) system of Mycobacterium tuberculosis, whose inhibition requires the concerted action of the antitoxin and its dedicated SecB-like chaperone. We show that the TAC toxin is a bona fide ribonuclease and identify exact cleavage sites in mRNA targets on a transcriptome-wide scale in vivo. mRNA cleavage by the toxin occurs after the second nucleotide of the ribosomal A-site codon during translation, with a strong preference for CCA codons in vivo. Finally, we report the cryo-EM structure of the ribosome-bound TAC toxin in the presence of native M. tuberculosis cspA mRNA, revealing the specific mechanism by which the TAC toxin interacts with the ribosome and the tRNA in the P-site to cleave its mRNA target.

Suggested Citation

  • Moise Mansour & Emmanuel Giudice & Xibing Xu & Hatice Akarsu & Patricia Bordes & Valérie Guillet & Donna-Joe Bigot & Nawel Slama & Gaetano D’urso & Sophie Chat & Peter Redder & Laurent Falquet & Lione, 2022. "Substrate recognition and cryo-EM structure of the ribosome-bound TAC toxin of Mycobacterium tuberculosis," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30373-w
    DOI: 10.1038/s41467-022-30373-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-30373-w
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-30373-w?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. Hatice Akarsu & Patricia Bordes & Moise Mansour & Donna-Joe Bigot & Pierre Genevaux & Laurent Falquet, 2019. "TASmania: A bacterial Toxin-Antitoxin Systems database," PLOS Computational Biology, Public Library of Science, vol. 15(4), pages 1-28, April.
    2. Patricia Bordes & Ambre Julie Sala & Sara Ayala & Pauline Texier & Nawel Slama & Anne-Marie Cirinesi & Valérie Guillet & Lionel Mourey & Pierre Genevaux, 2016. "Chaperone addiction of toxin–antitoxin systems," Nature Communications, Nature, vol. 7(1), pages 1-12, December.
    3. Valérie Guillet & Patricia Bordes & Cécile Bon & Julien Marcoux & Virginie Gervais & Ambre Julie Sala & Suzana Dos Reis & Nawel Slama & Israel Mares-Mejía & Anne-Marie Cirinesi & Laurent Maveyraud & P, 2019. "Structural insights into chaperone addiction of toxin-antitoxin systems," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    4. Prabhakar Tiwari & Garima Arora & Mamta Singh & Saqib Kidwai & Om Prakash Narayan & Ramandeep Singh, 2015. "MazF ribonucleases promote Mycobacterium tuberculosis drug tolerance and virulence in guinea pigs," Nature Communications, Nature, vol. 6(1), pages 1-13, May.
    5. Sandip Kaledhonkar & Ziao Fu & Kelvin Caban & Wen Li & Bo Chen & Ming Sun & Ruben L. Gonzalez & Joachim Frank, 2019. "Late steps in bacterial translation initiation visualized using time-resolved cryo-EM," Nature, Nature, vol. 570(7761), pages 400-404, June.
    6. Valérie Guillet & Patricia Bordes & Cécile Bon & Julien Marcoux & Virginie Gervais & Ambre Julie Sala & Suzana Reis & Nawel Slama & Israel Mares-Mejía & Anne-Marie Cirinesi & Laurent Maveyraud & Pierr, 2019. "Publisher Correction: Structural insights into chaperone addiction of toxin-antitoxin systems," Nature Communications, Nature, vol. 10(1), pages 1-1, December.
    7. Prabhakar Tiwari & Garima Arora & Mamta Singh & Saqib Kidwai & Om Prakash Narayan & Ramandeep Singh, 2015. "Correction: Corrigendum: MazF ribonucleases promote Mycobacterium tuberculosis drug tolerance and virulence in guinea pigs," Nature Communications, Nature, vol. 6(1), pages 1-1, November.
    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. Xibing Xu & Ben Usher & Claude Gutierrez & Roland Barriot & Tom J. Arrowsmith & Xue Han & Peter Redder & Olivier Neyrolles & Tim R. Blower & Pierre Genevaux, 2023. "MenT nucleotidyltransferase toxins extend tRNA acceptor stems and can be inhibited by asymmetrical antitoxin binding," Nature Communications, Nature, vol. 14(1), pages 1-18, 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. Xibing Xu & Ben Usher & Claude Gutierrez & Roland Barriot & Tom J. Arrowsmith & Xue Han & Peter Redder & Olivier Neyrolles & Tim R. Blower & Pierre Genevaux, 2023. "MenT nucleotidyltransferase toxins extend tRNA acceptor stems and can be inhibited by asymmetrical antitoxin binding," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Tannu Priya Gosain & Saurabh Chugh & Zaigham Abbas Rizvi & Neeraj Kumar Chauhan & Saqib Kidwai & Krishan Gopal Thakur & Amit Awasthi & Ramandeep Singh, 2024. "Mycobacterium tuberculosis strain with deletions in menT3 and menT4 is attenuated and confers protection in mice and guinea pigs," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Xiangkai Zhen & Yongyu Wu & Jinli Ge & Jiaqi Fu & Le Ye & Niannian Lin & Zhijie Huang & Zihe Liu & Zhao-qing Luo & Jiazhang Qiu & Songying Ouyang, 2022. "Molecular mechanism of toxin neutralization in the HipBST toxin-antitoxin system of Legionella pneumophila," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    4. Mikhail Metelev & Erik Lundin & Ivan L. Volkov & Arvid H. Gynnå & Johan Elf & Magnus Johansson, 2022. "Direct measurements of mRNA translation kinetics in living cells," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    5. Jonathan J. P. Peters & Tiarnan Mullarkey & Emma Hedley & Karin H. Müller & Alexandra Porter & Ali Mostaed & Lewys Jones, 2023. "Electron counting detectors in scanning transmission electron microscopy via hardware signal processing," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    6. Ritwika S. Basu & Michael B. Sherman & Matthieu G. Gagnon, 2022. "Compact IF2 allows initiator tRNA accommodation into the P site and gates the ribosome to elongation," Nature Communications, Nature, vol. 13(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_s41467-022-30373-w. 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.