The synucleins are a family of redox-active copper binding proteins.
Thermodynamic studies in conjunction with EPR confirm that α-synuclein, β-synuclein, and γ-synuclein bind copper(II) in a high affinity 1:1 stoichiometry. γ-Synuclein demonstrates the highest affinity, in the picomolar range, while α-synuclein and β-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 α-synuclein and position 65 in β-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.
Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA27AY, UK.
Paul
P
Davies
Xiaoyan
X
Wang
Claire J
CJ
Sarell
Alex
A
Drewett
Frank
F
Marken
John H
JH
Viles
David R
DR
Brown
D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D003300:Copper / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010084:Oxidation-Reduction; D011485:Protein Binding; D013816:Thermodynamics; D051844:alpha-Synuclein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051846:beta-Synuclein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051845:gamma-Synuclein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; D051844:alpha-Synuclein; D051846:beta-Synuclein; C023548:copper-binding protein; D051845:gamma-Synuclein; D003300:Copper