Copper Binding and Subsequent Aggregation of α‑Synuclein
Are Modulated by N‑Terminal Acetylation and Ablated by the
H50Q Missense Mutation
Version 4 2017-08-12, 13:14
Version 3 2016-11-28, 18:19
Version 2 2016-08-24, 17:19
Version 1 2016-08-18, 14:49
Posted on 2017-08-12 - 13:14
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, in vivo, 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.
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Mason, Rebecca
J.; Paskins, Aimee R.; Dalton, Caroline F.; Smith, David P. (2016). Copper Binding and Subsequent Aggregation of α‑Synuclein
Are Modulated by N‑Terminal Acetylation and Ablated by the
H50Q Missense Mutation. ACS Publications. Collection. https://doi.org/10.1021/acs.biochem.6b00708
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