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Hydralysins, a New Category of β-Pore-forming Toxins in Cnidaria

Cnidaria are venomous animals that produce diverse protein and polypeptide toxins, stored and delivered into the prey through the stinging cells, the nematocytes. These include pore-forming cytolytic toxins such as well studied actinoporins. In this work, we have shown that the non-nematocystic para...

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Published in:The Journal of biological chemistry 2005-06, Vol.280 (24), p.22847
Main Authors: Daniel Sher, Yelena Fishman, Mingliang Zhang, Mario Lebendiker, Ariel Gaathon, José-Miguel Mancheño, Eliahu Zlotkin
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container_issue 24
container_start_page 22847
container_title The Journal of biological chemistry
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creator Daniel Sher
Yelena Fishman
Mingliang Zhang
Mario Lebendiker
Ariel Gaathon
José-Miguel Mancheño
Eliahu Zlotkin
description Cnidaria are venomous animals that produce diverse protein and polypeptide toxins, stored and delivered into the prey through the stinging cells, the nematocytes. These include pore-forming cytolytic toxins such as well studied actinoporins. In this work, we have shown that the non-nematocystic paralytic toxins, hydralysins, from the green hydra Chlorohydra viridissima comprise a highly diverse group of β-pore-forming proteins, distinct from other cnidarian toxins but similar in activity and structure to bacterial and fungal toxins. Functional characterization of hydralysins reveals that as soluble monomers they are rich in β-structure, as revealed by far UV circular dichroism and computational analysis. Hydralysins bind erythrocyte membranes and form discrete pores with an internal diameter of ∼1.2 nm. The cytolytic effect of hydralysin is cell type-selective, suggesting a specific receptor that is not a phospholipid or carbohydrate. Multiple sequence alignment reveals that hydralysins share a set of conserved sequence motifs with known pore-forming toxins such as aerolysin, ϵ-toxin, α-toxin, and LSL and that these sequence motifs are found in and around the poreforming domains of the toxins. The importance of these sequence motifs is revealed by the cloning, expression, and mutagenesis of three hydralysin isoforms that strongly differ in their hemolytic and paralytic activities. The correlation between the paralytic and cytolytic activities of hydralysin suggests that both are a consequence of receptor-mediated pore formation. Hydralysins and their homologues exemplify the wide distribution of β-pore formers in biology and provide a useful model for the study of their molecular mode of action.
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title Hydralysins, a New Category of β-Pore-forming Toxins in Cnidaria
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