Structure and membrane actions of a marine worm protein cytolysin, Cerebratulus toxin A-III.
Four homologous Cerebratulus lacteus A toxins are the first and as yet only protein cytolysins to be isolated from an ancient phylum of marine worms, the nemertines. The most abundant and toxic variant, toxin A-III, has been sequenced and its mechanisms of action studied in the most detail. It consists of a single basic polypeptide chain of 95 amino acid residues cross-linked by three disulfide bonds, and possesses a predominantly alpha-helical secondary structure. The C-terminal third of the toxin sequence is postulated to be a helical 'hairpin' structure involved in pore formation. Toxin A-III permeabilizes a variety of cells as well as liposomes made from a variety of phospholipids; apparently large pores are formed, as large proteins are released almost as rapidly as small organic molecules and inorganic ions. At sublytic concentrations, the toxin also inhibits protein kinase C and endogenous voltage-gated cation selective (sodium, calcium) channels occurring in the nervous and cardiovascular systems. A curious observation, also reported for colicins and some other protein cytolysins, was the conservation of toxin secondary structure upon insertion into phospholipid liposomes, despite the strong likelihood that significant changes in tertiary structure occur to provide a hydrophobic surface for interaction with membrane lipids. Because of its small size and presumed single helical hairpin secondary structure, Cl toxin A-III is an excellent molecular subject for investigating protein insertion into biological membranes and mechanisms of pore formation.
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Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville 32610-0267.
D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000502:physiology; D003603:Cytotoxins / Q000737:chemistry / Q000633:toxicity*; D008387:Marine Toxins / Q000737:chemistry / Q000633:toxicity*; D008969:Molecular Sequence Data; D013329:Structure-Activity Relationship
C026601:Cerebratulus lacteus toxin A-III; D003603:Cytotoxins; D008387:Marine Toxins