Identification of the minimal copper(II)-binding alpha-synuclein sequence

Parkinson's disease has been long linked to environmental factors, such as transition metals and recently to alpha-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 alpha-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.