Role of the Gln/Glu residues of trichocellins A-II/B-II in ion-channel formation in lipid membranes and catecholamine secretion from chromaffin cells.
Trichocellins (TC) A-II and B-II, 20-residue peptaibols isolated from conidia of the fungus Trichoderma viride, have the same sequence except for the residue at position 18. Both TCs were found to form voltage-dependent ion-channels in bilayer lipid membranes (BLM) and to induce catecholamine secretion from bovine adrenal chromaffin cells through Ca2+ influx. TC-A-II (Gln18, neutral) was more effective than TC-B-II (Glu18, charged) for macroscopic current induction in BLMs and for catecholamine secretion from chromaffin cells, suggesting that Glu18 is unfavorable for the ion-channel formation in BLMs and chromaffin cell membranes. Nevertheless, single-channel recordings indicated that TC-B-II forms larger pores with longer open lifetimes than those of TC-A-II. This indicates that the negatively charged carboxyl group of Glu at position 18 stabilizes larger pores. The effects of the negative charge of Glu18 on the activities were confirmed by the use of a TC-B-II analog containing the methyl ester of Glu18.
Wada
S
S
Faculty of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Japan.
Iida
A
A
Asami
K
K
Tachikawa
E
E
Fujita
T
T
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects* / Q000378:metabolism; D018698:Glutamic Acid / Q000737:chemistry; D005973:Glutamine / Q000737:chemistry; D007473:Ion Channels / Q000096:biosynthesis* / Q000737:chemistry; D008051:Lipid Bilayers / Q000378:metabolism; D054848:Peptaibols; D010455:Peptides
D000900:Anti-Bacterial Agents; D002395:Catecholamines; D007473:Ion Channels; D008051:Lipid Bilayers; D054848:Peptaibols; D010455:Peptides; C106057:trichocellin; D005973:Glutamine; D018698:Glutamic Acid