IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-26562-8.html
   My bibliography  Save this article

Molecular architecture of black widow spider neurotoxins

Author

Listed:
  • Minghao Chen

    (Westfälische Wilhelms Universität Münster
    Max Planck Institute of Molecular Physiology)

  • Daniel Blum

    (Jacobs University Bremen)

  • Lena Engelhard

    (Max Planck Institute of Molecular Physiology)

  • Stefan Raunser

    (Max Planck Institute of Molecular Physiology)

  • Richard Wagner

    (Jacobs University Bremen)

  • Christos Gatsogiannis

    (Westfälische Wilhelms Universität Münster
    Max Planck Institute of Molecular Physiology)

Abstract

Latrotoxins (LaTXs) are presynaptic pore-forming neurotoxins found in the venom of Latrodectus spiders. The venom contains a toxic cocktail of seven LaTXs, with one of them targeting vertebrates (α-latrotoxin (α-LTX)), five specialized on insects (α, β, γ, δ, ε- latroinsectotoxins (LITs), and one on crustaceans (α-latrocrustatoxin (α-LCT)). LaTXs bind to specific receptors on the surface of neuronal cells, inducing the release of neurotransmitters either by directly stimulating exocytosis or by forming Ca2+-conductive tetrameric pores in the membrane. Despite extensive studies in the past decades, a high-resolution structure of a LaTX is not yet available and the precise mechanism of LaTX action remains unclear. Here, we report cryoEM structures of the α-LCT monomer and the δ-LIT dimer. The structures reveal that LaTXs are organized in four domains. A C-terminal domain of ankyrin-like repeats shields a central membrane insertion domain of six parallel α-helices. Both domains are flexibly linked via an N-terminal α-helical domain and a small β-sheet domain. A comparison between the structures suggests that oligomerization involves major conformational changes in LaTXs with longer C-terminal domains. Based on our data we propose a cyclic mechanism of oligomerization, taking place prior membrane insertion. Both recombinant α-LCT and δ-LIT form channels in artificial membrane bilayers, that are stabilized by Ca2+ ions and allow calcium flux at negative membrane potentials. Our comparative analysis between α-LCT and δ-LIT provides first crucial insights towards understanding the molecular mechanism of the LaTX family.

Suggested Citation

  • Minghao Chen & Daniel Blum & Lena Engelhard & Stefan Raunser & Richard Wagner & Christos Gatsogiannis, 2021. "Molecular architecture of black widow spider neurotoxins," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26562-8
    DOI: 10.1038/s41467-021-26562-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-26562-8
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-021-26562-8?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. Lin Tang & Tamer M. Gamal El-Din & Jian Payandeh & Gilbert Q. Martinez & Teresa M. Heard & Todd Scheuer & Ning Zheng & William A. Catterall, 2014. "Structural basis for Ca2+ selectivity of a voltage-gated calcium channel," Nature, Nature, vol. 505(7481), pages 56-61, January.
    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. Yue Li & Tian Yuan & Bo Huang & Feng Zhou & Chao Peng & Xiaojing Li & Yunlong Qiu & Bei Yang & Yan Zhao & Zhuo Huang & Daohua Jiang, 2023. "Structure of human NaV1.6 channel reveals Na+ selectivity and pore blockade by 4,9-anhydro-tetrodotoxin," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Rodrigo G. Fernandez Lahore & Niccolò P. Pampaloni & Enrico Schiewer & M.-Marcel Heim & Linda Tillert & Johannes Vierock & Johannes Oppermann & Jakob Walther & Dietmar Schmitz & David Owald & Andrew J, 2022. "Calcium-permeable channelrhodopsins for the photocontrol of calcium signalling," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    3. Guizhen Fan & Mariah R. Baker & Lara E. Terry & Vikas Arige & Muyuan Chen & Alexander B. Seryshev & Matthew L. Baker & Steven J. Ludtke & David I. Yule & Irina I. Serysheva, 2022. "Conformational motions and ligand-binding underlying gating and regulation in IP3R channel," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    4. Yiqing Wei & Zhuoya Yu & Lili Wang & Xiaojing Li & Na Li & Qinru Bai & Yuhang Wang & Renjie Li & Yufei Meng & Hao Xu & Xianping Wang & Yanli Dong & Zhuo Huang & Xuejun Cai Zhang & Yan Zhao, 2024. "Structural bases of inhibitory mechanism of CaV1.2 channel inhibitors," Nature Communications, Nature, vol. 15(1), pages 1-11, 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:12:y:2021:i:1:d:10.1038_s41467-021-26562-8. 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.