α-Synuclein is a small cytosolic protein of presynaptic nerve terminals composed of seven 11-residue repeats and a hydrophilic tail. α-Synuclein misfolding and dysfunction may contribute to the pathogenesis of Parkinson's disease and neurodegenerative dementias, but its normal folding and function are unknown. In solution, α-synuclein is natively unstructured but assumes an α-helical conformation upon binding to phospholipid membranes. We now show that this conformation of α-synuclein consists of two α-helical regions that are interrupted by a short break. The structural organization of the α-helices of α-synuclein was not anticipated by sequence analyses and may be important for its pathogenic role.
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