α-Synuclein-induced membrane remodeling is driven by binding affinity, partition depth, and interleaflet order asymmetry.

ABSTRACT: We have investigated the membrane remodeling capacity of the N-terminal membrane-binding domain of α-synuclein (α-Syn100). Using fluorescence correlation spectroscopy and vesicle clearance assays, we show that α-Syn100 fully tubulates POPG vesicles, the first demonstration that the amphipathic helix on its own is capable of this effect. We also show that at equal density of membrane-bound protein, α-Syn has dramatically reduced affinity for, and does not tubulate, vesicles composed of a 1:1 POPG:POPC mixture. Coarse-grained molecular dynamics simulations suggested that the difference between the pure POPG and mixture results may be attributed to differences in the protein's partition depth, the membrane's hydrophobic thickness, and disruption of acyl chain order. To explore the importance

SUBMITTER: Braun AR 

PROVIDER: S-EPMC4105054 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature