Identification of the Minimal Copper(II)-Binding α-Synuclein Sequence

Parkinson’s disease has been long linked to environmental factors, such as transition metals and recently to α-synuclein, a presynaptic protein. Using tryptophan-containing peptides, we identified the minimal Cu(II)-binding sequence to be within the first four residues, MDV(F/W), anchored by the α-amino terminus. In addition, mutant peptide 1−10 (Lys → Arg) verified that neither Lys6 nor Lys10 are necessary for Cu(II) binding. Interestingly, Trp4 excited-state decay kinetics measured for peptides and proteins reveal two quenching modes, possibly arising from two distinct Cu(II)−polypeptide structures.