Effect of pseudorepeat rearrangement on alpha-synuclein misfolding, vesicle binding, and micelle binding.

ABSTRACT: The pathological and physiological hallmarks of the protein alpha-synuclein (aS) are its misfolding into cytotoxic aggregates and its binding to synaptic vesicles, respectively. Both events are mediated by seven 11-residue amphiphilic pseudorepeats and, most generally, involve a transition from intrinsically unstructured conformations to structured conformations. Based on aS interactions with aggregation-inhibiting small molecules, an aS variant termed shuffled alpha-synuclein (SaS), wherein the first six pseudorepeats had been rearranged, was introduced. Here, the effects of this rearrangement on misfolding, vesicle binding, and micelle binding are examined in reference to aS and beta-synuclein to study the sequence characteristics underlying these processes. Fibrillization correlates wit

SUBMITTER: Rao JN 

PROVIDER: S-EPMC2731582 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature