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

MASON, Rebecca, PASKINS, Aimee, DALTON, Caroline and SMITH, David (2016). Copper Binding and Subsequent Aggregation of α-Synuclein Are Modulated by N-Terminal Acetylation and Ablated by the H50Q Missense Mutation. Biochemistry, 55 (34), 4737-4741.

Preview

PDF (Full license information can be found in the additional Information field below) Mason - Copper binding and subsequent aggregation (VoR).pdf - Published Version All rights reserved. Download (682kB) | Preview

Abstract

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

Item Type:	Article
Additional Information:	ACS AuthorChoice - This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. Further information about the license can be found under the publisher link
Research Institute, Centre or Group - Does NOT include content added after October 2018:	Biomedical Research Centre
Identification Number:	https://doi.org/10.1021/acs.biochem.6b00708
Page Range:	4737-4741
Depositing User:	Helen Garner
Date Deposited:	15 Dec 2016 14:27
Last Modified:	18 Mar 2021 04:08
URI:	https://shura.shu.ac.uk/id/eprint/14307

Actions (login required)

View Item

Downloads

Publication Metrics