Title
Opposite structural effects of epigallocatechin-3-gallate and dopamine binding to <tex>$\alpha$</tex>-synuclein Opposite structural effects of epigallocatechin-3-gallate and dopamine binding to <tex>$\alpha$</tex>-synuclein
Author
Faculty/Department
Faculty of Sciences. Chemistry
Publication type
article
Publication
Washington, D.C. ,
Subject
Chemistry
Source (journal)
Analytical chemistry. - Washington, D.C.
Volume/pages
88(2016) :17 , p. 8468-8475
ISSN
0003-2700
ISI
000382805900021
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
The intrinsically disordered and amyloidogenic protein α-synuclein (AS) has been linked to several neurodegenerative states, including Parkinsons 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 proteinligand 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.
Handle