Effect of EGCG On Fe(III)-induced conformational transition of silk fibroin, a model of protein related to neurodegenerative diseases.

Abstract:

:The abnormal aggregation of amyloid proteins is reported to play a critical role in the etiology of neurodegenerative disorders. Studies have shown that excessive ferric irons are associated with the misfolding of amyloid proteins, and that (-)-epigallocatechin gallate (EGCG) is a good metallic ion chelator with inhibitory effect on the aggregation of amyloid proteins. EGCG has been thus considered as a potential drug candidate for the treatment of neurodegenerative diseases. However, the mechanism of action for EGCG in inhibition of aggregation of amyloid proteins is still remaining unclear. Silk fibroin (SF) shares similarities with amyloid proteins in some amino acid sequences and fibrillation kinetics. In this work, therefore, we used SF as a model of protein to investigate the effects of Fe(III) and EGCG on conformational transition by using turbidity assay, thioflavin T (ThT) fluorescence spectroscopy, Raman spectroscopy, and atomic force microscope (AFM). We demonstrated that low concentration of Fe(III) ions promoted the formation of β-sheet conformers, while high concentration of Fe(III) ions inhibited further aggregation of SF. EGCG could significantly inhibit the conformational transition of SF when induced by Fe(III), and decrease the amount of β-sheet conformers dose-dependently. The findings provide important information regarding to EGCG as a potential agent for the prevention and treatment of neurodegenerative diseases. Fe(III) can accelerate the conformation transition of silk fibrion (SF) from random coil into β-sheet, while (-)-epigallocatechin gallate (EGCG) inhibits Fe(III)-induced β-sheet aggregation of SF., 2016. © 2015 Wiley Periodicals, Inc. Biopolymers 105: 100-107, 2016.

journal_name

Biopolymers

journal_title

Biopolymers

authors

Xu L,Tu S,Chen C,Zhao J,Zhang Y,Zhou P

doi

10.1002/bip.22752

subject

Has Abstract

pub_date

2016-02-01 00:00:00

pages

100-107

issue

2

eissn

0006-3525

issn

1097-0282

journal_volume

105

pub_type

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