IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-32690-6.html
   My bibliography  Save this article

Structure and dynamics of Toll immunoreceptor activation in the mosquito Aedes aegypti

Author

Listed:
  • Yoann Saucereau

    (University of Cambridge)

  • Thomas H. Wilson

    (University of Cambridge)

  • Matthew C. K. Tang

    (University of Cambridge)

  • Martin C. Moncrieffe

    (University of Cambridge)

  • Steven W. Hardwick

    (University of Cambridge)

  • Dimitri Y. Chirgadze

    (University of Cambridge)

  • Sandro G. Soares

    (University of Cambridge)

  • Maria Jose Marcaida

    (Ecole Polytechnique Fédérale de Lausanne)

  • Nicholas J. Gay

    (University of Cambridge)

  • Monique Gangloff

    (University of Cambridge)

Abstract

Aedes aegypti has evolved to become an efficient vector for arboviruses but the mechanisms of host-pathogen tolerance are unknown. Immunoreceptor Toll and its ligand Spaetzle have undergone duplication which may allow neofunctionalization and adaptation. Here we present cryo-EM structures and biophysical characterisation of low affinity Toll5A complexes that display transient but specific interactions with Spaetzle1C, forming asymmetric complexes, with only one ligand clearly resolved. Loop structures of Spaetzle1C and Toll5A intercalate, temporarily bridging the receptor C-termini to promote signalling. By contrast unbound receptors form head-to-head homodimers that keep the juxtamembrane regions far apart in an inactive conformation. Interestingly the transcriptional signature of Spaetzle1C differs from other Spaetzle cytokines and controls genes involved in innate immunity, metabolism and tissue regeneration. Taken together our results explain how upregulation of Spaetzle1C in the midgut and Toll5A in the salivary gland shape the concomitant immune response.

Suggested Citation

  • Yoann Saucereau & Thomas H. Wilson & Matthew C. K. Tang & Martin C. Moncrieffe & Steven W. Hardwick & Dimitri Y. Chirgadze & Sandro G. Soares & Maria Jose Marcaida & Nicholas J. Gay & Monique Gangloff, 2022. "Structure and dynamics of Toll immunoreceptor activation in the mosquito Aedes aegypti," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32690-6
    DOI: 10.1038/s41467-022-32690-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-32690-6
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-32690-6?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. Nikolaj Kulahin Roed & Cristina M. Viola & Ole Kristensen & Gerd Schluckebier & Mathias Norrman & Waseem Sajid & John D. Wade & Asser Sloth Andersen & Claus Kristensen & Timothy R. Ganderton & Johan P, 2018. "Structures of insect Imp-L2 suggest an alternative strategy for regulating the bioavailability of insulin-like hormones," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    2. Jules A. Hoffmann, 2003. "The immune response of Drosophila," Nature, Nature, vol. 426(6962), pages 33-38, November.
    3. Sarah E. Ewald & Bettina L. Lee & Laura Lau & Katherine E. Wickliffe & Guo-Ping Shi & Harold A. Chapman & Gregory M. Barton, 2008. "The ectodomain of Toll-like receptor 9 is cleaved to generate a functional receptor," Nature, Nature, vol. 456(7222), pages 658-662, December.
    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. Hai Ni & Yinuo Wang & Kai Yao & Ling Wang & Jiancheng Huang & Yongfang Xiao & Hongyao Chen & Bo Liu & Cliff Y. Yang & Jijun Zhao, 2024. "Cyclical palmitoylation regulates TLR9 signalling and systemic autoimmunity in mice," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Diana Boraschi & Dongjie Li & Yang Li & Paola Italiani, 2021. "In Vitro and In Vivo Models to Assess the Immune-Related Effects of Nanomaterials," IJERPH, MDPI, vol. 18(22), pages 1-16, November.
    3. Cristina M. Viola & Orsolya Frittmann & Huw T. Jenkins & Talha Shafi & Pierre Meyts & Andrzej M. Brzozowski, 2023. "Structural conservation of insulin/IGF signalling axis at the insulin receptors level in Drosophila and humans," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    4. Srujan Kumar Dondapati & Georg Pietruschka & Lena Thoring & Doreen A Wüstenhagen & Stefan Kubick, 2019. "Cell-free synthesis of human toll-like receptor 9 (TLR9): Optimization of synthesis conditions and functional analysis," PLOS ONE, Public Library of Science, vol. 14(4), pages 1-16, April.

    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_s41467-022-32690-6. 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.