alpha-Synuclein and beta-Amyloid form a Bridged Copper Complex

作者：Drew Simon C

来源：Applied Magnetic Resonance, 2015, 46(9): 1041-1052.

DOI：10.1007/s00723-015-0662-7

The deposition of insoluble beta-amyloid (A beta) peptide into extracellular senile plaques is a pathological hallmark of Alzheimer's disease. Fragmented alpha-synuclein (alpha Syn) and a relatively high concentration of Cu2+ ions are found within amyloid deposits. Both A beta and alpha Syn bind Cu2+ with an apparent dissociation constant in the sub-nanomolar range at physiological pH, fuelling speculation that deleterious redox chemistry and metal-mediated protein misfolding may contribute to disease progression. Binary Cu(A beta) and Cu(alpha Syn) complexes have been extensively studied, although the Cu2+ coordination of heterogeneous mixtures of A beta and alpha Syn has yet to be characterised. This study used synthetic N-terminal fragments A beta 1-16 and alpha Syn1-56 to reveal a new Cu(alpha Syn)(A beta) coordination mode anchored upon a 5,6-membered chelate supplied by Met1-Asp2 of alpha Syn, with the fourth equatorial ligand being supplied by a His side chain of A beta.

• 出版日期2015-9