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Alamethicin and related peptaibols — model ion channels

Abstract

Peptaibols are considered as models of those ion channels which consist of a bundle of transbilayer helices surrounding a central pore. X-Ray diffraction and NMR studies have yielded high resolution structures for several peptaibols. In conjunction with other spectroscopic investigations and molecular dynamics simulations, these studies suggest that peptaibols form proline-kinked α-helices, and that there may be “hinge-bending” movement of the helix in the region of the central proline residue. The amphipathicity of peptaibol helices is analyzed in relation to their channel-forming properties. Studies of the interactions of peptaibols with lipid bilayers suggest that they are helical when in a membrane-like environment, and that the helix orientation relative to the bilayer is sensitive to the peptaibol: lipid ratio, and to the degree of hydration of the bilayer. Electrical studies reveal that many peptaibols form multiple-conductance level channels in a voltage-dependent fashion. Analysis of conductance levels provides support for the “barrel stave” model of channel formation, whereby different conductance levels correspond to different numbers of monomers in a helix bundle. Alternative models for voltage-activation are discussed, and the roles of molecular dipoles and of hinge-bending in this process are considered. Two molecular models for an N = 6 bundle of alamethicin helices are presented and their electrostatic properties analyzed. The relevance of studies of peptaibols to channel and transport proteins in general is considered.

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Abbreviations

Aib:

α-amino-isobutyric acid

Alm:

alamethicin

ATR-FTIR:

attenuated total reflection Fourier transform infrared

CD:

circular dichroism

CFP:

channel-forming peptide

Chol:

cholesterol

diPhyPC:

diphytanoyl phosphatidylcholine

DMPC:

dimyristoyl phosphatidylcholine

DOPC:

dioleoyl phosphatidylcholine

DOPE:

dioleoyl phosphatidylethanolamine

DPPS:

dipahnitoyl phosphatidylserine

DTPC:

ditetradecyl phosphatidylcholine

HSM:

hydrophilic surface map

I-V:

current-voltage

MLV:

multilamellar vesicle

nAChR:

nicotinic acetylcholine receptor

P:L:

protein-to-lipid ratio

POPC:

palmitoyloleoyl phosphatidylcholine

SUV:

small unilamellar vesicle

Zrv:

zervamicin

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Sansom, M.S.P. Alamethicin and related peptaibols — model ion channels. Eur Biophys J 22, 105–124 (1993). https://doi.org/10.1007/BF00196915

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Key words

  • Ion channel
  • Peptaibol
  • Channel-forming peptide
  • Molecular modelling