Membrane channel forming polypeptides. Molecular conformation and mitochondrial uncoupling activity of antiamoebin,an a-aminoisobutyric acid containing peptide

The conformations of the 16-residue fungal peptide antiamoebin I were studied in DMSO soln. by 1- and 2-dimensional NMR techniques. A substantial no. of resonances in the 270-MHz 1H NMR spectrum were assigned. Intramolecularly H-bonded (solvent inaccessible) NH groups were identified by detg. solvent and temp.dependence of NH chem.shifts and rates of H-D exchange.Ten backbone NH groups are inaccessible to solvent, whereas 3 NH groups assigned to phenylalanine-1, aminoisobutyrate-2, and -8 residues are exposed to solvent.The NMR results,together with the stereochem.constraints imposed by the presence of a-aminoisobutyryl, isovalyl, prolyl, and 4-hydroxypropyl residues, favor a highly ordered structure. Two backbone conformations consistent with the data are considered. Antiamoebin is shown to be an effective uncoupler of oxidative phosphorylation in rat liver mitochondria, providing evidence for its membrane-modifying activity