Copper Binding and Subsequent Aggregation of α‑Synuclein Are Modulated by N‑Terminal Acetylation and Ablated by the H50Q Missense Mutation

Published on 2017-08-12T13:14:20Z (GMT) by
The Parkinson’s disease-associated protein α-synuclein exhibits significant conformational heterogeneity. Bacterially expressed α-synuclein is known to bind to copper, resulting in the formation of aggregation-prone compact conformations. However, <i>in vivo</i>, α-synuclein undergoes acetylation at its N-terminus. Here the effect of this modification and the pathological H50Q mutation on copper binding and subsequent conformational transitions were investigated by electrospray ionization–ion mobility spectrometry–mass spectrometry. We demonstrate that acetylation perturbs the ability of α-synuclein to bind copper and that the H50Q missense mutation in the presence of N-terminal acetylation prevents copper binding. These modifications and mutations prevent the formation of the most compact conformations and inhibit copper-induced aggregation.

Cite this collection

Mason, Rebecca

J.; Paskins, Aimee R.; Dalton, Caroline F.; Smith, David P. (2017): Copper Binding and Subsequent Aggregation of α‑Synuclein

Are Modulated by N‑Terminal Acetylation and Ablated by the

H50Q Missense Mutation. ACS Publications.

https://doi.org/10.1021/acs.biochem.6b00708

Retrieved: 14:47, Oct 19, 2017 (GMT)