title: Charged or aromatic anchor residue dependence of transmembrane peptide tilt.
abstract: The membrane-spanning segments of integral membrane proteins often are flanked by aromatic or charged amino acid residues, which may "anchor" the transmembrane orientation. Single spanning transmembrane peptides such as those of the WALP family, acetyl-GWW(LA)(n)LWWA-amide, furthermore adopt a moderate average tilt within lipid bilayer membranes. To understand the anchor residue dependence of the tilt, we introduce Leu-Ala "spacers" between paired anchors and in some cases replace the outer tryptophans. The resulting peptides, acetyl-GX(2)ALW(LA)(6)LWLAX(22)A-amide, have Trp, Lys, Arg, or Gly in the two X positions. The apparent average orientations of the core helical sequences were determined in oriented phosphatidylcholine bilayer membranes of varying thickness using solid-state (2)H NMR spectroscopy. When X is Lys, Arg, or Gly, the direction of the tilt is essentially constant in different lipids and presumably is dictated by the tryptophans (Trp(5) and Trp(19)) that flank the inner helical core. The Leu-Ala spacers are no longer helical. The magnitude of the apparent helix tilt furthermore scales nicely with the bilayer thickness except when X is Trp. When X is Trp, the direction of tilt is less well defined in each phosphatidylcholine bilayer and varies up to 70° among 1,2-dioleoyl-sn-glycero-3-phosphocholine, 1,2-dimyristoyl-sn-glycero-3-phosphocholine, and 1,2-dilauroyl-sn-glycero-3-phosphocholine bilayer membranes. Indeed, the X = Trp case parallels earlier observations in which WALP family peptides having multiple Trp anchors show little dependence of the apparent tilt magnitude on bilayer thickness. The results shed new light on the interactions of arginine, lysine, tryptophan, and even glycine at lipid bilayer membrane interfaces.
authors.affiliation: Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas 72701, USA.
authors.forename: Vitaly V
authors.initials: VV
authors.lastname: Vostrikov
authors.forename: Anna E
authors.initials: AE
authors.lastname: Daily
authors.forename: Denise V
authors.initials: DV
authors.lastname: Greathouse
authors.forename: Roger E
authors.initials: RE
authors.lastname: Koeppe
mesh_terms: D024322:Amino Acids, Aromatic / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry*; D017433:Protein Structure, Secondary
chemical_list: D024322:Amino Acids, Aromatic; D008051:Lipid Bilayers; D009842:Oligopeptides; D010713:Phosphatidylcholines