alamethicin and antiamoebin

Kinks or bends introduced in peptides and proteins by "helical distorter" residues such as proline, other imino acids and glycine, especially when these are in close proximity in the sequence, are increasingly recognized as playing an essential role in the gating of channel-forming peptides as well as of physiological ion channels. Peptaibols are useful simple models for the much more complex biological ion channels, especially voltage-gated ones. In this short review, we compare the monomeric structures of three selected peptaibols (alamethicin, trichotoxin and antiamoebin) that widely differ with regards their near-central kink angles and dipolar moment orientations. These structural features are then shown to be correlated to the different patterns of channel activity, both at the macroscopic and single-channel levels of investigation.

Topics: Alamethicin; Antimicrobial Cationic Peptides; Electrophysiology; Ion Channels; Kinetics; Lipid Bilayers; Models, Molecular; Peptaibols; Peptides; Protein Structure, Secondary

Antiamoebin is a member of the peptaibol family of polypeptides 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.. The structure of antiamoebin I has been determined by X-ray crystallography at 1.4 A resolution. The molecule forms a helical structure, which, as a result of the presence of a number of proline and hydroxyproline residues, has a deep bend in the middle. Circular dichroism spectroscopy, single-channel conductance studies and fluorescence diffusion studies suggest a mode of ion transport that is entirely different from that of the other two members of the peptaibol family (alamethicin and zervamicin) whose structures and functions have been examined in detail.. The structure of the polypeptide has been determined and a functional model for its mode of action in membranes is presented. Although under some conditions antiamoebin may form ion channels, unlike the closely related alamethicin and zervamicin polypeptides, its major membrane-modifying activity appears to be as an ion carrier.

Topics: Alamethicin; Amebicides; Anti-Bacterial Agents; Carrier Proteins; Circular Dichroism; Crystallography, X-Ray; Membranes; Models, Chemical; Models, Molecular; Peptaibols; Peptides; Proline

The effect of different representatives of the group of peptaibiotics, alpha-amino-isobutyric acid rich secondary metabolites of filamentous fungi, on Culex pipiens larvae was studied. Light and transmission electron microscopy techniques were used to localize the intracellular damage and to determine the target organells for the mode of action of peptaibols in mosquito larvae. Though different in insecticidal activity, all tested compounds induced the same type of tissue damage, which was characterized by heavy challenge of mitochondria followed by partial swelling, crystaeolysis and destruction of mitochondrial walls. It is concluded that the mode of action of peptaibols in mosquito larvae is mediated through the damage of mitochondria. The structure-mosquitocidal effect of these compounds, their potential mode of action and role in the natural fungal entomopathogenic process are briefly discussed.

Topics: Alamethicin; Amino Acid Sequence; Aminoisobutyric Acids; Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Culicidae; Fungi; Insecticides; Intercellular Signaling Peptides and Proteins; Larva; Mitochondria; Molecular Sequence Data; Organic Chemicals; Peptaibols; Peptides; Peptides, Cyclic