A helical-dipole model describes the single-channel current rectification of an uncharged peptide ion channel.

Abstract

We are deigning simple peptide ion channels as model sstems for the study of the physical principles controlling conduction through Ion-channel proteins. Here we report on an uncharg peptide, Ac-(Leu-Ser-Ser-Leu-LeuSer-Leu)3-CONH2, de to form an aggregate of parale, amphiphilic, membrane-snuing a-helices around a central water-filed pore. This peptide in planar lipid bilayers forms ion channels that show singl-hannel current rectification in smmetrnc 1 M KCI. The current at a given holding membrane potential is larger than the current measured through the same channel when the potential is reversed. Based on our hypothesized gating mechm, the larger currents flow from the peptide carboxyl terminus-toward the amino terminus. We present an Ionic electrodiffusion model based on the helicaldipole potential and the dielectric interfacial polarization energy, which with reasonable values for dipole magnitude and dielecic constants, accurately replicates the current-voltage data.Many aspects of signal transduction and transmission in living cells depend on ionic currents, which flow into or out of the cell through ion-channel proteins. The currents of several types of channel have an asymmetric dependence on the transmembrane potential; if the larger current is directed toward the cell interior, the channel is said to be inwardly rectifying. Whole-cell rectification, arising from the summed currents of many individual channels, can arise from a difference in the channel opening-closing equilibrium at positive and negative membrane potentials (asymmetric voltage gating). However, a single open channel can also show rectification. This rectification can be caused by asymmetries in Mg2+ blocking (1-3), permeant ion concentration (4, 5), and fixed electrical charges or dipoles at the membrane surface or in the channel (6).Both fixed charges and dipoles are likely to affect conduction in ion-channel proteins. Charge effects have been demonstrated in the nicotinic acetylcholine receptor, where single-channel conductance and rectification properties depend on the charge of certain amino acid side chains thought to be near the conducting pore (7). However, the effect of dipoles on conduction has not been as clearly demonstrated, even though they could be important in pores lined by a-helices. The dipole moments of the peptide bonds in an a-helix add together to form an electrical macrodipole (8,9). Transmembrane a-helices are major structural features of membrane proteins such as bacteriorhodopsin (10) and the photosynthetic reaction center (11) and are thought to line the pores of ion channels such as the gapjunction (12, 13) and the nicotinic receptor (14). [Dipoles might also influence rectification in channels without a-helices, such as certain forms of the model channel gramicidin (15,16).]We are using minimalist-designed peptide ion channels to study the physical principles underlying conduction through protein ion channels. To study purely dipolar effects on rectification, we have designed and synthesized an unc...

Inversion of Membrane Surface Charge by Trivalent Cations Probed with a Cation-Selective Channel

“…The asymmetry was either an inherent property of the channel 43–49 or was introduced by a gradient of acidity across the membrane 50, 51 . The rectification factor calculated as the ratio of the current in the higher conductance branch of the I/V characteristic to the current at the opposite polarity at ±100 mV reaches about 5.0 or smaller values 50, 51 .…”

Peptide‐dominated membranes preceding the genetic takeover by RNA: latest thinking on a classic controversy

“…During wet-dry cycling on clay, even dipeptides of histidyl-histidine showed some catalytic enhancement, (50) and certain lone-helix peptides can indeed self-assemble to biologically active transmembrane clusters, such as antimicrobial peptides, (51) or repetitive model peptides [Ac-(LSSLLSL) 3 -CONH 2 ] surrounding a central channel. (52,53) Similarly, polar pockets drawn partly into the lipophilic core of a prebiotic membrane could have constituted the first metabolically active protoenzymes. In particular, b-hairpins are studied systematically as small functional model peptides, (54) some of which have been selected for binding ATP with high affinity.…”

Coarse-grained molecular dynamics simulations of membrane proteins and peptides

“…To explore a simple interfacial peptide we modelled and simulated LS3, a synthetic leucine/serine-containing peptide with sequence (LSSLLSL) 3 , which has been studied in detail by DeGrado and colleagues (Åkerfeldt et al, 1993;Dieckmann et al, 1999;Kienker et al, 1994;Lear et al, 1988Lear et al, , 1994Lear et al, , 1997. LS3 has been demonstrated to form anhelix which adopts an interfacial location parallel to the bilayer surface when monomeric.…”