Alamethicin and related peptaibols--model ion channels.
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 alpha-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.
Sansom
M S
MS
Laboratory of Molecular Biophysics, University of Oxford, UK.
D000408:Alamethicin / Q000737:chemistry*; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry; D004563:Electrochemistry; D004594:Electrophysiology; D007473:Ion Channels / Q000737:chemistry* / Q000502:physiology; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry; D008954:Models, Biological; D008969:Molecular Sequence Data; D054848:Peptaibols; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D013816:Thermodynamics; D014961:X-Ray Diffraction
D000900:Anti-Bacterial Agents; D007473:Ion Channels; D008051:Lipid Bilayers; D054848:Peptaibols; D010455:Peptides; D000408:Alamethicin; C077077:zervamicin IIB