Modulation of α-Synuclein Aggregation by Cytochrome c Binding and Hetero-dityrosine Adduct Formation.

Abstract:

:The aggregation of α-synuclein (α-Syn) has been implicated strongly in Parkinson's disease (PD). The intrinsically disordered nature of α-Syn makes this protein prone to self-association or heteroassociation with another protein or lipid. While conformational fluctuation and free radical chemistry have been shown to play important roles in its ability toward self- and heteroassociation, any systematic understanding of their contributions is missing. Here, we report an in vitro investigation of the interaction between α-Syn and cytochrome c in the oxidized (cyt c III) and reduced forms (cyt c II), in which cyt c III was found to induce a large compaction of α-Syn and inhibit the aggregation by favoring a hetero-dityrosine bond formation. In contrast, the presence of cyt c II did not result in any compaction and its presence was found to facilitate α-Syn aggregation. The variation in the charge distribution of the surface residues of cyt c III and cyt c II is expected to play a decisive role in their interaction with α-Syn.

journal_name

ACS Chem Neurosci

authors

Ghosh S,Mahapatra A,Chattopadhyay K

doi

10.1021/acschemneuro.8b00393

subject

Has Abstract

pub_date

2019-03-20 00:00:00

pages

1300-1310

issue

3

issn

1948-7193

journal_volume

10

pub_type

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