Peptide environment specifies conformation. Helicity of hydrophobic segments compared in aqueous, organic, and membrane environments.
Transmembrane segments in integral membrane proteins exist characteristically as helices in lipid bilayers, yet are often rich in residues considered helix-destabilizing (Val, Ile, Gly) in soluble proteins. We propose that helicity of a transmembrane segment is likely to be affected by factors other than the "intrinsic" helical propensities of its component amino acids. This hypothesis is tested by comparing the conformation(s) in aqueous, organic, membrane-mimetic (micellar), and membrane (bilayer) environments of designed model peptides with systematically altered helical propensity and/or segmental hydrophobicity. Peptides of prototypic sequence NH2-(Ser-Lys)2-Ala5-Leu6-Ala7-Ala8-Leu9-Ala10-++ +Trp11-Ala12-Leu13-Ala14- (Lys-Ser)3-OH were synthesized, which incorporate a hydrophobic core "guest" segment (residues 5-14) into a water-soluble hydrophilic host matrix. Related peptides featured substitution of Leu6,9,13-->Gly, Leu6,9,13-->Ala, and Ala7,10,14-->Gly. Circular dichroism spectra revealed that algorithms for soluble proteins correctly predicted peptide helical proclivities in aqueous solutions, but peptide helicity in organic (trifluoroethanol) solvents, membrane-mimetic SDS micelles, and negatively charged lipid bilayer vesicles, was found to be governed almost exclusively by the segmental hydrophobicity of the peptide mid-hydrophobic core segment. In related Trp fluorescence studies, peptide-membrane association was similarly correlated with extent of hydrophobic interaction.
Li
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SC
Division of Biochemistry Research, Hospital for Sick Children, Toronto, Ontario, Canada.
Deber
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CM
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D008051:Lipid Bilayers / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry*; D008567:Membranes, Artificial; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D010539:Permeability; D010712:Phosphatidic Acids / Q000737:chemistry; D010715:Phosphatidylglycerols / Q000737:chemistry; D017433:Protein Structure, Secondary; D012995:Solubility; D012997:Solvents
D008051:Lipid Bilayers; D008565:Membrane Proteins; D008567:Membranes, Artificial; D010455:Peptides; D010712:Phosphatidic Acids; D010715:Phosphatidylglycerols; D012997:Solvents