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 Vol. 280; no. 24; p. 22847 |
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| Main Authors: | , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
American Society for Biochemistry and Molecular Biology
17-06-2005
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| Online Access: | Get full text |
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| Summary: | 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 â¼1.2 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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| ISSN: | 0021-9258 1083-351X |
| DOI: | 10.1074/jbc.M503242200 |