Ion channels formed by amphipathic helical peptides

Abstract

Channel forming peptides (CFPs) are amphipathic peptides, of length ca. 20 residues, which adopt an alpha-helical conformation in the presence of lipid bilayers and form ion channels with electrophysiological properties comparable to those of ion channel proteins. We have modelled CFP channels as bundles of parallel trans-bilayer helices surrounding a central ion-permeable pore. Ion-channel interactions have been explored via accessible surface area calculations, and via evaluation of changes in van der Waals and electrostatic energies as a K+ ion is translated along the length of the pore. Two CFPs have been modelled: (a) zervamicin-A1-16, a synthetic apolar peptaibol related to alamethicin, and (b) delta-toxin from Staphylococcus aureus. Both of these CFPs have previously been shown to form ion channels in planar lipid bilayers, and have been shown to have predominantly helical conformations. Zervamicin-A1-16 channels were modelled as bundles of 4 to 8 parallel helices. Two related helix bundle geometries were explored. K(+)-channel interactions have been shown to involve exposed backbone carbonyl oxygen atoms. delta-Toxin channels were modelled as bundles of 6 parallel helices. Residues Q3, D11 and D18 generate favourable K(+)-channel interactions. Rotation of W15 about its C beta-C gamma bond has been shown to be capable of occluding the central pore, and is discussed as a possible model for sidechain conformational changes in relation to ion channel gating.

Structural Dissection and In Vivo Effectiveness of a Peptide Inhibitor of Porphyromonas gingivalis Adherence to Streptococcus gordonii

“…In this study, we show that the EXXP motif located upstream of VXXLL in BAR also contributes to the interaction of Mfa with (1,15,35,36). In these proteins, the Pro residue confers a kink within an ␣-helical region, and Sansom et al (30,31) suggested that an acidic residue at position Ϫ3 from Pro may function in cation binding. Consistent with this, Duan et al (13) showed that the S. gordonii antigen I/II protein, SspB, binds calcium and that the BAR region of antigen I/II was necessary for cation binding activity.…”

A virtual instrumentation based protocol for the automated implementation of the inner field compensation method

“…Additional arguments that can be employed to rationalize the departure of the kinetics shown in Fig. 3, panel a, from a simple mono-exponential-like curve stem from the fact that even in the absence of the potential difference across the lipid membrane, the alamethicin peptide adopts two kinds of orientations: a tilted orientation at the membrane-aqueous solution interface, and a more fully transmembrane-inserted orientation, with the N terminal almost reaching to the trans side of the membrane [25,26]. Although the alamethicin monomers in this latter orientation are very unlikely to attain the 'critical concentration' needed generate transmembrane conductive oligomers, they may also contribute to the overall changes of the dipole potential (Δp) of the membrane.…”

Packing interactions of aib‐containing helices: Molecular modeling of parallel dimers of simple hydrophobic helices and of alamethicin

“…For interhelix restraints, dTARGET = 9.4 A in all models. An asymmetric biharmonic potential able in several studies of TM helix bundles, 13, 24 and is comparable to that employed by Nilges and Briinger in simulations of GCN4 helix dimen2' …”