Quinopeptide formation associated with the disruptive effect of epigallocatechin-gallate on lysozyme fibrils.
Numerous studies demonstrate that natural polyphenols can inhibit amyloid formation and disrupt preformed amyloid fibrils. In the present study, the fibril-disruptive effects of epigallocatechin-3-gallate (EGCG) were examined using lysozyme as a model protein. The results indicated that EGCG dose dependently inhibited lysozyme fibrillation and modified the peptide chains with quinonoid moieties under acidic conditions, as measured by ThT fluorescence, transmission electron microscopy, and an NBT-staining assay. Moreover, EGCG transformed the preformed lysozyme fibrils to amorphous aggregates through quinopeptide formation. The thiol blocker, N-ethylmaleimide, inhibited the disruptive effect of EGCG on preformed fibrils, suggesting that thiol groups are the binding sites for EGCG. We propose that the formation of quinone intermediates via oxidation and subsequent binding to lysozyme chains are the main processes driving the inhibition of amyloid formation and disruption of preformed fibrils by EGCG. The information presented in this study may provide fresh insight into the link between the antioxidant capacity and anti-amyloid activity of polyphenols.
Key Laboratory of Analytical Chemistry for Life Science of Shaanxi Province, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an 710119, China.
Na
N
Cao
Key Laboratory of Analytical Chemistry for Life Science of Shaanxi Province, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an 710119, China.
Yu-Jie
YJ
Zhang
School of Chemical Engineering, Guizhou Institute of Technology, Guiyang 550003, China.
Shuang
S
Feng
Key Laboratory of Analytical Chemistry for Life Science of Shaanxi Province, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an 710119, China. Electronic address: chengmingzeng@snnu.edu.cn.
Cheng-Ming
CM
Zeng
D000682:Amyloid / Q000737:chemistry; D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D009113:Muramidase / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D059808:Polyphenols / Q000737:chemistry / Q000494:pharmacology; D066263:Protein Aggregation, Pathological
D000682:Amyloid; D010455:Peptides; D059808:Polyphenols; D002392:Catechin; C045651:epigallocatechin gallate; C421864:hen egg lysozyme; D009113:Muramidase
Amyloid fibrils; Epigallocatechin-3-gallate; Quinopeptides