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.
Laboratory of Molecular Biophysics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-8013, USA.
Mark S
MS
Jackson
Jennifer C
JC
Lee
D000595:Amino Acid Sequence; D001665:Binding Sites; D002384:Catalysis; D003300:Copper / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding / Q000502:physiology; D021241:Spectrometry, Mass, Electrospray Ionization; D014364:Tryptophan / Q000378:metabolism; D051844:alpha-Synuclein / Q000737:chemistry* / Q000235:genetics
D010455:Peptides; D051844:alpha-Synuclein; D003300:Copper; D014364:Tryptophan