7PTY

Delta-latroinsectotoxin dimer

7PTY の概要

• エントリーDOI: 10.2210/pdb7pty/pdb
• 関連するPDBエントリー: 7PTY
• EMDBエントリー: 13642 13643
• 分子名称: Delta-latroinsectotoxin-Lt1a (1 entity in total)
• 機能のキーワード: pore-forming toxin, toxin
• 由来する生物種: Latrodectus tredecimguttatus (Mediterranean black widow spider, Latrodectus mactans tredecimguttatus)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 290095.09

構造登録者

Chen, M.,Gatsogiannis, C. (登録日: 2021-09-27, 公開日: 2021-12-08, 最終更新日: 2024-07-17)

主引用文献

Chen, M.,Blum, D.,Engelhard, L.,Raunser, S.,Wagner, R.,Gatsogiannis, C.
Molecular architecture of black widow spider neurotoxins.
Nat Commun, 12:6956-6956, 2021

PubMed 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 Ca-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 Ca 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.

PubMed: 34845192
DOI: 10.1038/s41467-021-26562-8

実験手法

ELECTRON MICROSCOPY (4.63 Å)