title: Equilibrium and non-equilibrium conformations of peptides in lipid bilayers.
abstract: A synthetic, hydrophobic, 27-amino-acid-residue peptide 'K27', modelled on the trans-membrane domain of the slow voltage-gated potassium channel, IsK, has been incorporated into a lipid bilayer and its conformational properties studied using FT-IR spectroscopy. The conformation following reconstitution is found to be dependent on the nature of the solvent employed. When the reconstitution is conducted by solvent evaporation from a methanol solution, aggregates comprised of beta-strands are stabilised and their concentration is essentially invariant with time. By contrast, when trifluoroethanol is used, the initial conformation of the peptide is alpha-helical. This then relaxes to an equilibrium state between alpha-helices and beta-strands. The alpha-helix-to beta-strand conversion rate is relatively slow, and this allows the kinetics to be studied by FT-IR spectroscopy. The reverse process is much slower but again can be demonstrated by FT-IR. Thus, it appears that a true equilibrium structure can only be achieved by starting with peptide in the alpha-helical conformation. We believe this result should be of general validity for hydrophobic peptide reconstitution. The implications for conformational changes in membrane proteins are discussed.
authors.affiliation: Centre for Self-Organising Molecular Systems, University of Leeds, UK.
authors.forename: N
authors.initials: N
authors.lastname: Boden
authors.forename: Y
authors.initials: Y
authors.lastname: Cheng
authors.forename: P F
authors.initials: PF
authors.lastname: Knowles
mesh_terms: D000595:Amino Acid Sequence; D004134:Dimyristoylphosphatidylcholine; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D015221:Potassium Channels / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013055:Spectrophotometry, Infrared; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D008051:Lipid Bilayers; D010455:Peptides; D015221:Potassium Channels; D004134:Dimyristoylphosphatidylcholine