Effect of Bilayer Phospholipid Composition and Curvature on Ligand Transfer by the α-Tocopherol Transfer Protein

We report here our preliminary investigations on the mechanism of α-TTP-mediated ligand transfer as assessed using fluorescence resonance energy transfer (FRET) assays. These assays monitor the movement of the model α-tocopherol fluorescent derivative ((R)-2,5,7,8-tetramethyl-chroman-2-[9-(7-nitro-benzo[1,2,5]oxadiazol-4-yl amino)-nonyl]-chroman-6-ol; NBD-Toc) from protein to acceptor vesicles containing the fluorescence quencher TRITC-PE. We have found that α-TTP utilizes a collisional mechanism of ligand transfer requiring direct protein–membrane contact, that rates of ligand transfer are greater to more highly curved lipid vesicles, and that such rates are insensitive to the presence of anionic phospholipids in the acceptor membrane. These results point to hydrophobic features of α-TTP dominating the binding energy between protein and membrane. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. An erratum to this article can be found at