Role of proline residue in the channel-forming and catecholamine-releasing activities of the peptaibol, trichosporin-B-VIa

AbstractTrichosporin-B-VIa (TS-B-VIa) has a Pro14-kinked helical structure which is considered to be important for the formation of peptaibol-type ion-channels in lipid bilayer membranes. TS-B-VIa and its analog [Aid14]TS-B-VIa with Pro → Aib substitution at position 14, resulting in a straight helical structure, were tested for ion-channel-forming activity in planar lipid bilayer membranes and for ability to induce catecholamine secretion from cultured bovine adrenal chromaffin cells. Voltage-dependent multi-channel conductance, which is characteristic of TS-B-VIa, was also observed for [Aid14]TS-B-VIa. In single-channel measurements, current fluctuations induced by [Aid14]TS-B-VIa had a shorter life-time and showed fewer substates than those induced by TS-B-VIa. Catecholamine secretion induced by these peptides at low concentrations is completely Ca2+-dependent. At high concentrations, TS-B-VIa-induced secretion was partly independent of external Ca 2+, but this was not the case for the analog. The differences of behavior can be explained in terms of the differences of hydrophobicity, amphiphilicity, and magnitude of dipole moment due to the conformational changes around position 14 and the C-terminal domain caused by the Pro → Aib substitution