Abstract
Antiamoebin (AAM) is a polypeptide antibiotic that is capable of forming ion channels in phospholipid membranes; planar bilayer studies have suggested the channels are octamers. The crystal structure of a monomeric form of AAM has provided the basis for molecular modelling of an octameric helical bundle channel. The channel model is funnelβshaped due to a substantial bend in the middle of the polypeptide chain caused by the presence of several imino acids. Interβmonomer hydrogen bonds orientate a ring of glutamine side chains to form a constriction in the pore lumen. The channel lumen is lined both by side chains of Gln11 and by polypeptide backbone carbonyl groups. Electrostatic calculations on the model are compatible with a channel that transports cations across membranes.
The AAM channel model is compared with the crystal structures of two bacterial (KcsA and MthK) potassium channels. AAM and the potassium channels exhibit common functional features, such as cationβselectivity and similar single channel conductances. Common structural features include being multimers, each formed from a bundle of eight transmembrane helices, with lengths roughly comparable to the thickness of lipid bilayers. In addition, they all have aromatic amino acids that lie at the bilayer interfaces and which may aid in the stabilization of the transmembrane helices, as well as narrower constrictions that define the ion binding sites or selectivity filters in the pore lumen. The commonality of structural and functional features in these channels thus suggests that antiamoebin is a good, simple model for more complex bacterial and eukaryotic ion channels, capable of providing insight into details of the mechanisms of ion transport and multimeric channel stability. Copyright Β© 2003 European Peptide Society and John Wiley & Sons, Ltd.