Ion Mobility Mass Spectrometry Studies of the Inhibition of Alpha Synuclein Amyloid Fibril Formation by (–)-Epigallocatechin-3-Gallate
Yanqin Liu A , Lam H. Ho A , John. A. Carver A and Tara L. Pukala A B
+ Author Affiliations
- Author Affiliations
A School of Chemistry and Physics, The University of Adelaide, Adelaide, SA 5005, Australia.
B Corresponding author. Email: tara.pukala@adelaide.edu.au
Australian Journal of Chemistry 64(1) 36-40 https://doi.org/10.1071/CH10334
Submitted: 10 September 2010 Accepted: 10 November 2010 Published: 14 January 2011
Abstract
Ion mobility-mass spectrometry (IM-MS) is emerging as an important biophysical technique for the structural analysis of proteins and their assemblies, in particular for structurally heterogeneous systems such as those on the protein misfolding and aggregation pathway. Using IM-MS we have monitored amyloid fibril formation of A53T α-synuclein, a mutant synuclein protein associated with Parkinson’s disease, and identified that a conformational change towards a more compact structure occurs during the initial stages of aggregation. Binding of A53T α-synuclein to a flavenoid based amyloid fibril inhibitor, (–)-epigallocatechin-3-gallate, has been observed with a 1:1 stoichiometry. By analysis of ion collision cross-sections, we show epigallocatechin gallate binding prevents protein conformational change, and in turn decreases the formation of fibrillar aggregates.
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