The History of Alamethicin: A Review of the Most Extensively Studied Peptaibol

Recent Results in Alamethicin Research

“…by László Kredics [1] presented a historical overview about research on alamethicin (ALM), discussing the discovery, primary structure, biosynthetic pathway, structural and conformational properties, channel formation and biological activities of ALM and its synthetic analogues.…”

“…As summarized by Leitgeb et al [1], ALM has a predominantly α-helical conformation with a small distortion in the structure generated by the Pro residue at the 14 th position, which is referred to as proline-kinked α-helical conformation. ALM is capable of binding to the surface of lipid bilayers and insertion into the membranes, which is depending on a series of parameters like elasticity, structure and hydration level of the lipid bilayer, peptide concentration, peptide/lipid molar ratio as well as temperature [1].…”

Mechanical properties of lipid bilayers and regulation of mechanosensitive function

“…101 In general, they bind to microbial membranes, forming lipid pores and can elicit cell lysis at high concentrations. [102][103][104] Alamethicin, melittin, MG-H2 (a magainin analog) and piscidin bind strongly and stabilize preformed lipidic pores. 105 Thus, it is reasonable to assume that inclusion of these kind of peptides alleviates tension by adsorbing to the high-curved edges of lipidic pores.…”

“…[113][114][115] Alm is a hydrophobic peptaibol (20-residues) that adopts predominantly helical conformations, whose degree of helicity and conformational flexibility depends on several biophysical factors such as temperature, lipid composition, physical state of lipids, membrane hydration, salt content, pH, and the peptide-to-lipid (P/L) molar ratio. 103,[114][115][116] Channel formation by Alm has been explained through parallel "TM helical bundles" or "barrel staves" composed of several membrane spanning peptides that aggregate to line an aqueous pore, 103,104 although it has been proposed that Alm inserts into bilayers using also a "toroidal" mechanism when it is exposed to ether-linked phospholipids. 116 Nevertheless, folding and oligomerization of Alm are seriously affected if ether lipids are used instead of ester-linked lipids.…”

“…Indeed, hexameric Alm channels are more stable than other assemblages. 103 This can be done by the integration of the internal tension that is associated with the membrane thinning derived from the creation of a lipidic pore. Depending on lipid composition, at this specific value, peptides start to change their orientation with respect to the membrane plane from a parallel-to-perpendicular arrangement.…”