Alamethicin and related membrane channel forming polypeptides.
Alamethicin and several related microbial polypeptides, which contain a high proportion of alpha-aminoisobutyric acid (Aib) residues, possess the ability to modify the permeability properties of phospholipid bilayer membranes. Alamethicin induces excitability phenomena in model membranes and has served as an excellent model for the study of voltage sensitive transmembrane channels. This review summarizes various aspects of the structural chemistry and membrane modifying properties of alamethicin and related Aib containing peptides. The presence of Aib residues in these sequences, constrains the polypeptides to 3(10) or alpha-helical conformations. Functional membrane channels are formed by aggregation of cylindrical peptide helices, which span the lipid bilayer, forming a scaffolding for an aqueous column across the membrane. After consideration of the available data on the conductance characteristics of alamethicin channels, a working hypothesis for a channel model is outlined. Channel aggregates in the lipid phase may be stabilized by intermolecular hydrogen bonding, involving a central glutamine residue and also by interactions between the macro-dipoles of proximate peptide helices. Fluctuations between different conductance states are rationalized by transitions between states of different aggregation and hence altered dimensions of the aqueous core or by changes in net dipole moment of the aggregate. Ion fluxes through the channel may also be affected by the electric field within the aqueous core.
D000408:Alamethicin; D000595:Amino Acid Sequence; D000621:Aminoisobutyric Acids; D000900:Anti-Bacterial Agents; D006860:Hydrogen Bonding; D007473:Ion Channels / Q000502:physiology*; D008081:Liposomes; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D014475:Uncoupling Agents / Q000494:pharmacology
D000621:Aminoisobutyric Acids; D000900:Anti-Bacterial Agents; D007473:Ion Channels; D008081:Liposomes; D046911:Macromolecular Substances; D008565:Membrane Proteins; D014475:Uncoupling Agents; C100049:2-aminoisobutyric acid; D000408:Alamethicin