Mechanism of an animal toxin-antidote system

Caro, L.; Wei, A. D.; Thomas, C. A.; Posch, G.; Uremis, A.; Franzi, M. C.; Abell, S. J.; Laszlo, A. H.; Gundlach, J. H.; Ramirez, J.-M.; Ailion, M.

doi:10.1101/2024.06.11.598564

bioRxiv · 10.1101/2024.06.11.598564

Mechanism of an animal toxin-antidote system

Caro, L.·Wei, A. D.·Thomas, C. A.·Posch, G.·Uremis, A.·Franzi, M. C.·Abell, S. J.·Laszlo, A. H.·Gundlach, J. H.·Ramirez, J.-M.·Ailion, M.

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Abstract

Toxin-antidote systems are selfish genetic elements composed of a linked toxin and antidote. The peel-1 zeel-1 toxin-antidote system in C. elegans consists of a transmembrane toxin protein PEEL-1 which acts cell autonomously to kill cells. Here we investigate the molecular mechanism of PEEL-1 toxicity. We find that PEEL-1 requires a small membrane protein, PMPL-1, for toxicity. Together, PEEL-1 and PMPL-1 are sufficient for toxicity in a heterologous system, HEK293T cells, and cause cell swelling and increased cell permeability to monovalent cations. Using purified proteins, we show that PEEL-1 and PMPL-1 allow ion flux through lipid bilayers and generate currents which resemble ion channel gating. Our work suggests that PEEL-1 kills cells by co-opting PMPL-1 and creating a cation channel.

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Caro, L., Wei, A. D., Thomas, C. A., Posch, G., Uremis, A., Franzi, M. C., Abell, S. J., Laszlo, A. H., Gundlach, J. H., Ramirez, J.-M., Ailion, M.. 2024-06-13. Mechanism of an animal toxin-antidote system. https://doi.org/10.1101/2024.06.11.598564

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