pH dependent insertion of a diphtheria toxin B fragment peptide into the lipid membrane: a conformational analysis |
| |
| Authors: | R Brasseur V Cabiaux P Falmagne J M Ruysschaert |
| |
| Affiliation: | 1. Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA 30322, United States;2. Department of Chemistry, Emory University and Georgia Institute of Technology, Atlanta, GA 30322, United States;3. College of Engineering and Applied Sciences, Nanjing University, Nanjing, Jiangsu Province 210093, China;1. Departamento de Farmacologia e Toxicologia, Instituto Nacional de Controle de Qualidade em Saúde, Fundação Oswaldo Cruz (INCQS/FIOCRUZ), Avenida Brasil 4365, 21040-900 Rio de Janeiro, RJ, Brazil;2. Departamento de Farmacologia, Escola Paulista de Medicina, Universidade Federal de São Paulo (EPM/UNIFESP), Rua Três de Maio 100, 04044-020 São Paulo, SP, Brazil;3. Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (FMRP/USP), Av. Bandeirantes, 3900, 14049-900 Ribeirão Preto, SP, Brazil |
| |
| Abstract: | 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. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
