THE STRUCTURE AND FUNCTION OF ANTIAMEBIN-I, A PROLINE-RICH MEMBRANE-ACTIVE POLYPEPTIDE

Background: Antiamoebin is a member of the peptaibol family of polypep tides and has a unique antibiotic activity: it acts as an antiamoebic agent, but does not effectively haemolyze erythrocytes even though it does exhibit membrane-modifying activity. Results: The structure of an tiamoebin I has been determined by X-ray crystallography at 1.4 Angstr om resolution. The molecule forms a helical structure, which, as a res ult of the presence of a number of proline and hydroxyproline residues , has a deep bend in the middle. Circular dichroism spectroscopy, sing le-channel conductance studies and fluorescence diffusion studies sugg est a mode of ion transport that is entirely different from that of th e other two members of the peptaibol family (alamethicin and zervamici n) whose structures and functions have been examined in detail. Conclu sions: The structure of the polypeptide has been determined and a func tional model for its mode of action in membranes is presented. Althoug h under some conditions antiamoebin may form ion channels, unlike the closely related alamethicin and zervamicin polypeptides, its major mem brane-modifying activity appears to be as an ion carrier.