Insight into α-synuclein plasticity and misfolding from differential micelle binding.

ABSTRACT: Misfolded species of the 140-residue protein α-synuclein (αS) are implicated in the demise of dopaminergic neurons, resulting in fatal neurodegeneration. The intrinsically unstructured protein binds curved synaptic vesicle membranes in helical conformations but misfolds into amyloid fibrils via β-sheet interactions. Breaks in helical αS conformation may offer a pathway to transition from helical to sheet conformation. Here, we explore the evolution of broken αS helix conformations formed in complex with SDS and SLAS micelles by molecular dynamics simulations. The population distribution of experimentally observed αS conformations is related to the spatial concentration of intrinsic micelle shape perturbations. For the success of micelle-induced αS folding, we posit the length of the first

SUBMITTER: Mazumder P 

PROVIDER: S-EPMC3946565 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature