Konijnenberg, A, Ranica, S, Narkiewicz, J et al. (4 more authors) (2016) Opposite Structural Effects of Epigallocatechin-3-gallate and Dopamine Binding to α-Synuclein. Analytical Chemistry, 88 (17). pp. 8468-8475. ISSN 0003-2700
Abstract
The intrinsically disordered and amyloidogenic protein α-synuclein (AS) has been linked to several neurodegenerative states, including Parkinson's disease. Here, nanoelectrospray-ionization mass spectrometry (nano-ESI-MS), ion mobility (IM), and native top-down electron transfer dissociation (ETD) techniques are employed to study AS interaction with small molecules known to modulate its aggregation, such as epigallocatechin-3-gallate (EGCG) and dopamine (DA). The complexes formed by the two ligands under identical conditions reveal peculiar differences. While EGCG engages AS in compact conformations, DA preferentially binds to the protein in partially extended conformations. The two ligands also have different effects on AS structure as assessed by IM, with EGCG leading to protein compaction and DA to its extension. Native top-down ETD on the protein-ligand complexes shows how the different observed modes of binding of the two ligands could be related to their known opposite effects on AS aggregation. The results also show that the protein can bind either ligand in the absence of any covalent modifications, such as oxidation.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | This document is the Accepted Manuscript version of a Published Work that appeared in final form in Konijnenberg, A, Ranica, S, Narkiewicz, J, Legname, G, Grandori, R, Sobott, F and Natalello, A (2016) Opposite Structural Effects of Epigallocatechin-3-gallate and Dopamine Binding to α-Synuclein. Analytical Chemistry, 88 (17). pp. 8468-8475. ISSN 0003-2700 © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/acs.analchem.6b00731 |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 27 Sep 2016 12:54 |
Last Modified: | 03 Nov 2017 04:52 |
Published Version: | http://dx.doi.org/10.1021/acs.analchem.6b00731 |
Status: | Published |
Publisher: | American Chemical Scciety |
Identification Number: | 10.1021/acs.analchem.6b00731 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:105252 |