Tertiary Contact Formation in α-Synuclein Probed by Electron Transfer

Abstract

To explore tertiary contact formation in α-synuclein, a natively unfolded protein implicated in Parkinson's disease, we have measured the rates of reaction between a powerful electron donor, the tryptophan (W) triplet excited state, and an acceptor, 3-nitro-tyrosine (Y(NO_2)) in six different variants, probing loop sizes between 15 and 132 residues. Electron transfer rates decrease with loop size with the fastest contact time of 140 ns for the N-terminal pair and the slowest of 1.2 μs for the N- to C-terminal pair. Diffusion coefficients ranging from ∼2 × 10^(-6) to ∼10^(-5) cm^2 s^(-1) were extracted from simultaneous fits of the W to Y(NO_2) electron (triplet excited state) and energy transfer (singlet excited state) kinetics.