title: The pH-dependent induction of lipid membrane ionic permeability by N-terminally lysine-substituted analogs of gramicidin A.
abstract: Insertion of charged groups at the N-terminus of the gramicidin A (gA) amino acid sequence is considered to be fatal for  peptide channel-forming activity because of hindrance to the head-to-head dimer formation. Here the induction of ionic conductivity in planar bilayer lipid membranes (BLM) was studied with gA analogs having lysine either in the first ([Lys1]gA) or the third ([Lys3]gA) position. If added to the bathing solution at neutral or acidic pH, these analogs, being protonated and thus positively charged, were unable to induce ionic current across BLM. By contrast, at pH 11 the induction of BLM conductivity was observed with both lysine-substituted analogs. Based on the dependence of the macroscopic current on the side of the peptide addition, sensitivity to calcium ions and susceptibility to sensitized photoinactivation, as well as on the single-channel properties of the analogs, we surmise that at alkaline pH [Lys1]gA formed channels with predominantly single-stranded structure of head-to-head helical dimers, whereas [Lys3]gA open channels had the double-stranded helical structure. CD spectra of the lysine-substituted analogs in liposomes were shown to be pH-dependent.
authors: A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, 119991, Russia.
authors: Tatyana I
authors: TI
authors: Rokitskaya
authors: Alexandra I
authors: AI
authors: Sorochkina
authors: Sergey I
authors: SI
authors: Kovalchuk
authors: Natalya S
authors: NS
authors: Egorova
authors: Elena A
authors: EA
authors: Kotova
authors: Sergey V
authors: SV
authors: Sychev
authors: Yuri N
authors: YN
authors: Antonenko
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects*; D004553:Electric Conductivity; D006096:Gramicidin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D008239:Lysine / Q000737:chemistry; D008969:Molecular Sequence Data
chemical_list: D008051:Lipid Bilayers; D006096:Gramicidin; D008239:Lysine