Structure and functional divergence of the non-canonical BoNT-like toxin PG1 and PG2
In the authors' words
Botulinum neurotoxins (BoNTs) are potent bacterial toxins. Distinct BoNT-like toxins, including BoNT/X, BoNT/En, and PMP1, form a distinct lineage. Here we characterize two additional members of this group, PG-toxin 1 and 2 (PG1 and PG2). Their light-chain (LC) and heavy-chain (HC) domains are encoded by adjacent genes. PG1 and PG2 LCs cleave Drosophila SNAP-25 at distinct sites (N196-E197 and R191-K193, respectively); PG1 is more potent, while PG2 activity depends on pH and ionic strength. Both LCs enter Sf9 cells via clathrin-mediated endocytosis. PG1 LC is toxic to Drosophila and northern armyworm independently of its HC, whereas PG2 LC toxicity is enhanced by its HC. Cryo-EM shows that PG1 adopts a distinct compact di-chain architecture with a door-hinge-like “belt.” These findings expand the structural and functional diversity of the BoNT family and support the potential of PG-toxins as insecticidal agents and research tools. Here the authors characterise two botulinum-like toxins, PG1 and PG2. Their light chains cut a key protein in fruit flies; PG1 is toxic even without its heavy chain. PG1 has a distinct compact structure. These findings expand toxin knowledge and suggest potential as insecticides or research tools.
Appeared: Thursday, September 24. Nature Communications. Peer-reviewed journal.