Copper coordination by familial mutants of parkinson's disease-associated α-synuclein

Abstract

α-Synuclein (αS) is a small natively unfolded protein whose interactions with Cu2+ have been proposed to play a role in Parkinson's disease (PD). We recently studied the Cu2+ coordination of recombinant human αS using electron paramagnetic resonance spectroscopy and identified two coordination modes at physiological pH, one anchored upon the amino terminus (mode 1) and the other anchored upon the side chain of His50 (mode 2). Here we report the Cu2+Coordination of the A30P, E46K and A53T mutants associated with inherited forms of PD. At physiological pH, the same two Cu2+ coordination modes were adopted by each of the familial mutants. The spectrum of Cu2+/αS(A53T) was very similar to the sp..