title: 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.
authors.affiliation: Department of Macromolecular Science, State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai, 200433, China.
authors.forename: Lihui
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Macromolecular Science, State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai, 200433, China.
authors.forename: Sidong
authors.initials: S
authors.lastname: Tu
authors.affiliation: Department of Macromolecular Science, State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai, 200433, China.
authors.forename: Congheng
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Macromolecular Science, State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai, 200433, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Medicine, St Vincent's Hospital, the University of Melbourne, Fitzroy, Victoria, 3065, Australia.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Macromolecular Science, State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai, 200433, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
keywords: EGCG; Fe(III); neurodegenerative diseases; silk fibroin