title: The 21-residue surfactant peptide (LysLeu4)4Lys(KL4) is a transmembrane alpha-helix with a mixed nonpolar/polar surface.
abstract: The 21-residue peptide KLLLLKLLLLKLLLLKLLLLK (KL4) has been synthesized and analyzed regarding its secondary structure and orientation in lipid environments. Fourier transform infrared and circular dichroism spectroscopy shows that the peptide exhibits approximately 80% alpha-helical content both in dodecylphosphocholine micelles and in 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)/phosphatidylglycerol (PG) 7:3 (w/w) bilayers. The positively charged lysine residues are evenly distributed over the entire, otherwise nonpolar, circumference of the helix. This is in sharp contrast to the uneven distribution of polar and nonpolar residues in amphipathic helices. Fourier transform infrared spectroscopy of the peptide inserted in DPPC/PG bilayers shows that the helical axis is oriented parallel to the lipid acyl chains. These data do not support a previous hypothesis that the KL4 peptide interacts with peripheral parts of a phospholipid monolayer and mimics the pulmonary surfactant protein SP-B, which is composed of several amphipathic alpha-helices. KL4 accelerates the spreading of phospholipid mixtures at an air/water interface but does so less efficiently than other transmembranous helical polypeptides studied.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Gustafsson
authors.forename: G
authors.initials: G
authors.lastname: Vandenbussche
authors.forename: T
authors.initials: T
authors.lastname: Curstedt
authors.forename: J M
authors.initials: JM
authors.lastname: Ruysschaert
authors.forename: J
authors.initials: J
authors.lastname: Johansson
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine; D000388:Air; D000595:Amino Acid Sequence; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002942:Circular Dichroism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008051:Lipid Bilayers; D008823:Micelles; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D010715:Phosphatidylglycerols; D010767:Phosphorylcholine / Q000031:analogs & derivatives; D017433:Protein Structure, Secondary; D012997:Solvents; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D014867:Water
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C097558:KL4 surfactant; D008051:Lipid Bilayers; D008823:Micelles; D010455:Peptides; D010715:Phosphatidylglycerols; D012997:Solvents; D014867:Water; D010767:Phosphorylcholine; D015060:1,2-Dipalmitoylphosphatidylcholine; C028810:dodecylphosphocholine