title: Hydralysins, a new category of beta-pore-forming toxins in cnidaria.
abstract: 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 beta-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 beta-structure, as revealed by far UV circular dichroism and computational analysis. Hydralysins bind erythrocyte membranes and form discrete pores with an internal diameter of approximately 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, epsilon-toxin, alpha-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 beta-pore formers in biology and provide a useful model for the study of their molecular mode of action.
authors.affiliation: Department of Cell and Animal Biology, Silberman Institute of Life Sciences, Hebrew University, Jerusalem, Israel.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sher
authors.forename: Yelena
authors.initials: Y
authors.lastname: Fishman
authors.forename: Mingliang
authors.initials: M
authors.lastname: Zhang
authors.forename: Mario
authors.initials: M
authors.lastname: Lebendiker
authors.forename: Ariel
authors.initials: A
authors.lastname: Gaathon
authors.forename: José-Miguel
authors.initials: JM
authors.lastname: Mancheño
authors.forename: Eliahu
authors.initials: E
authors.lastname: Zlotkin
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002241:Carbohydrates / Q000737:chemistry; D002942:Circular Dichroism; D003001:Cloning, Molecular; D003063:Cnidaria; D003064:Cnidarian Venoms / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D004910:Erythrocyte Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D006829:Hydra; D013058:Mass Spectrometry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation; D009498:Neurotoxins / Q000737:chemistry*; D009995:Osmosis; D010743:Phospholipids / Q000737:chemistry; D052899:Pore Forming Cytotoxic Proteins; D011487:Protein Conformation; D020033:Protein Isoforms; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D012984:Software; D014118:Toxins, Biological / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: D002241:Carbohydrates; D003064:Cnidarian Venoms; D009498:Neurotoxins; D010743:Phospholipids; D052899:Pore Forming Cytotoxic Proteins; D020033:Protein Isoforms; D011994:Recombinant Proteins; D014118:Toxins, Biological; C478478:hydralysin