title: Paradoxical one-ion pore behavior of the long β-helical peptide of marine cytotoxic polytheonamide B.
abstract: The cytotoxic 48-mer peptide, polytheonamide B (pTB), from a marine sponge forms a β(6.3)-helix with an inner diameter of 4 Å and a length of 45 Å, features that allow the selective permeation of monovalent cations across targeted cell membranes. To characterize this long, narrow pore, electrophysiological examination using a planar lipid bilayer method was performed. The single-channel current amplitude exhibited saturation for concentrated Cs(+) or K(+) solution, and the reversal potential in mixed solutions did not exhibit any anomalous mole-fraction behavior. These results suggest the one-ion permeation mechanism. This is in contrast to the short (26 Å) β(6.3)-helical gramicidin channel, which holds two ions simultaneously. The paradoxical one-ion permeation through the long pTB channel was modeled with a discrete-state Markov model. Ions permeate through the channel by stepping between two binding sites in the pore, but never occupy these sites simultaneously in either pure or mixed ion solution.
authors.affiliation: Department of Molecular Physiology and Biophysics, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Iwamoto
authors.affiliation: Laboratory of Aquatic Natural Products Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, 113-8657, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Matsunaga
authors.affiliation: Department of Molecular Physiology and Biophysics, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan.
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Oiki
mesh_terms: D001665:Binding Sites; D002586:Cesium / Q000737:chemistry; D047908:Intracellular Signaling Peptides and Proteins; D008051:Lipid Bilayers; D008390:Markov Chains; D008962:Models, Theoretical; D010446:Peptide Fragments / Q000494:pharmacology*; D011188:Potassium / Q000737:chemistry; D011506:Proteins / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008051:Lipid Bilayers; D010446:Peptide Fragments; D011506:Proteins; C111717:polytheonamide B; D002586:Cesium; D011188:Potassium