The synucleins are a family of redox-active copper binding proteins

Thermodynamic studies in conjunction with EPR confirm that alpha-synuclein, beta-synuclein, and gamma-synuclein bind copper(II) in a high affinity 1:1 stoichiometry. gamma-Synuclein demonstrates the highest affinity, in the picomolar range, while alpha-synuclein and beta-synuclein both bind copper(II) with nanomolar affinity. The copper center on all three proteins demonstrates reversible or partly reversible redox cycling. Various mutations show that the primary coordinating ligand for copper(II) is located within the N-terminal regions between residues 2-9. There is also a contribution from the C-terminus in conjunction with the histidine at position 50 in alpha-synuclein and position 65 in beta-synuclein, although these regions appear to have little effect on overall coordination stability. These histidines and the C-terminus, however, appear to be critical to the redox engine of the proteins.