The mechanism of channel formation by alamethicin as viewed by molecular dynamics simulations.
Alamethicin is a 20-residue channel-forming peptide that forms a stable amphipathic alpha-helix in membrane and membrane-mimetic environments. This helix contains a kink induced by a central Gly-X-X-Pro sequence motif. Alamethicin channels are activated by a cis positive transbilayer voltage. Channel activation is suggested to correspond to voltage-induced insertion of alamethicin helices in the bilayer. Alamethicin forms multi-conductance channels in lipid bilayers. These channels are formed by parallel bundles of transmembrane helices surrounding a central pore. A change in the number of helices per bundle switches the single channel conductance level. Molecular dynamics simulations of alamethicin in a number of different environments have been used to explore its channel-forming properties. These simulations include: (i) alamethicin in solution in water and in methanol; (ii) a single alamethicin helix at the surface of a phosphatidylcholine bilayer; (iii) single alamethicin helices spanning a phosphatidylcholine bilayer; and (iv) channels formed by bundles of 5, 6, 7 or 8 alamethicin helices spanning a phosphatidylcholine bilayer. The total simulation time is c. 30 ns. Thus, these simulations provide a set of dynamic snapshots of a possible mechanism of channel formation by this peptide.
Sansom
M S
MS
Department of Biochemistry, University of Oxford, UK.
Tieleman
D P
DP
Berendsen
H J
HJ
D000408:Alamethicin / Q000737:chemistry*; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D003198:Computer Simulation; D007473:Ion Channels; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary
D000900:Anti-Bacterial Agents; D007473:Ion Channels; D000408:Alamethicin