pH dependent insertion of a diphtheria toxin B fragment peptide into the lipid membrane: a conformational analysis.
A peptide of diphtheria toxin B fragment (residues 147-266) has been shown to induce pore formation in lipid bilayer membranes at low pH. Such an effect was obtained at a much lower extent or not at all at pH = 7. The region localized between residues 225 and 246 is highly hydrophobic (27.3% polarity) and characterized by a high concentration of proline residues. Since proline cis-trans isomerization is highly sensitive to the pH of the medium, we investigated the capability of the cis and trans isomers to penetrate into the lipid matrix. Obviously, the cis-trans isomerization of proline 242 and 245, assumed to be imposed by a low pH, uncovers the hydrophobic region and induces its insertion into a lipid layer of dipalmitoylphosphatidylcholine. The lipid matrix destabilization resulting from this process could promote the penetration into the lipid bilayer of an amphipatic structure (153-178) similar to the transverse lipid associating domains of membrane proteins.
D004167:Diphtheria Toxin / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008051:Lipid Bilayers / Q000378:metabolism*; D008958:Models, Molecular; D010446:Peptide Fragments / Q000378:metabolism; D011392:Proline; D011663:Pulmonary Surfactants
D004167:Diphtheria Toxin; D008051:Lipid Bilayers; D010446:Peptide Fragments; D011663:Pulmonary Surfactants; C039171:diphtheria toxin fragment B; D011392:Proline