title: Conformation of alamethicin in phospholipid vesicles: implications for insertion models.
abstract: The secondary structure of alamethicin, a membrane channel-forming polypeptide, has been examined by circular dichroism spectroscopy to determine the relationship of its conformation in organic solution to its conformation in a membrane-bound state. The spectrum of alamethicin in small unilamellar dimyristoyl phosphatidylcholine vesicles is significantly different from its spectrum in 10% methanol/acetonitrile, the solvent from which it was crystallized (Fox and Richards: Nature 300:325-330, 1982), as well as its spectrum in methanol, the solvent in which NMR studies have been done (Banerjee and Chan: Biochemistry 22:3709-3713, 1983). This suggests that structural models based on studies of the molecule in organic solvents may not be entirely appropriate for the membrane-bound state. To distinguish between different models for channel formation and insertion, two different methods were used to associate the alamethicin with vesicles; in addition, the effect of oligomerization on the conformation of the membrane-bound state was investigated. These studies are consistent with a modified insertion model in which alamethicin monomers, dimers, or trimers associate with the bilayer and then spontaneously oligomerize to form a prechannel with a higher helix content. This aggregate could then "open" upon application of an appropriate gating transmembrane potential.
authors.affiliation: Department of Chemistry, Rensselaer Polytechnic Institute, Troy, New York 12180.
authors.forename: M
authors.initials: M
authors.lastname: Cascio
authors.forename: B A
authors.initials: BA
authors.lastname: Wallace
mesh_terms: D000408:Alamethicin; D000900:Anti-Bacterial Agents; D002942:Circular Dichroism; D004134:Dimyristoylphosphatidylcholine; D007202:Indicators and Reagents; D008051:Lipid Bilayers; D008081:Liposomes; D008962:Models, Theoretical; D008968:Molecular Conformation; D011487:Protein Conformation
chemical_list: D000900:Anti-Bacterial Agents; D007202:Indicators and Reagents; D008051:Lipid Bilayers; D008081:Liposomes; D000408:Alamethicin; D004134:Dimyristoylphosphatidylcholine