title: Association of a pH-sensitive peptide with membrane vesicles: role of amino acid sequence.
abstract: The solution properties and bilayer association of two synthetic 30 amino acid peptides, GALA and LAGA, have been investigated at pH 5 and 7.5. These peptides have the same amino acid composition and differ only in the positioning of glutamic acid and leucine residues which together compose 47% of each peptide. Both peptides undergo a similar coil to helix transition as the pH is lowered from 7.5 to 5.0. However, GALA forms an amphipathic alpha-helix whereas LAGA does not. As a result, GALA partitions into membranes to a greater extent than LAGA and can initiate leakage of vesicle contents and membrane fusion which LAGA cannot (Subbarao et al., 1987; Parente et al., 1988). Membrane association of the peptides has been studied in detail with large phosphatidylcholine vesicles. Direct binding measurements show a strong association of the peptide GALA to vesicles at pH 5 with an apparent Ka around 10(6). The single tryptophan residue in each peptide can be exploited to probe peptide motion and positioning within lipid bilayers. Anisotropy changes and the quenching of tryptophan fluorescence by brominated lipids in the presence of vesicles also indicate that GALA can interact with uncharged vesicles in a pH-dependent manner. By comparison to the peptide LAGA, the membrane association of GALA is shown to be due to the amphipathic nature of its alpha-helical conformation at pH 5.
authors: Department of Pharmacy, School of Pharmacy, University of California, San Francisco 94143.
authors: R A
authors: RA
authors: Parente
authors: L
authors: L
authors: Nadasdi
authors: N K
authors: NK
authors: Subbarao
authors: F C
authors: FC
authors: Szoka
mesh_terms: D000595:Amino Acid Sequence; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000378:metabolism*; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D010539:Permeability / Q000187:drug effects
chemical_list: D008081:Liposomes; D010455:Peptides; C066951:GALA peptide; C066952:LAGA