Interference of EGCG on the Zn(II)-induced conformational transition of silk fibroin as a model protein related to neurodegenerative diseases

Misfolding or amyloid beta-sheet aggregation of specific proteins is considered to be an underlying pathogenic mechanism of neurodegenerative diseases, such as Alzheimer's disease (AD). Some metallic ions, such as Zn(II), have been reported to promote the conformational transition of neurodegenerative disease-related proteins, whereas (-)-epigallocatechine gallate (EGCG) displays an inhibitory effect on the aggregation of those proteins. Few studies have investigated the secondary structure changes of those pathological proteins affected by Zn(II), EGCG and their co-existence. In the present work we used silk fibroin (SF), which has a similar conformational transition mechanism to neurodegenerative diseases-related proteins, as a model protein to reveal the influence of Zn(II) and EGCG on the SF conformation and the interference of EGCG on the Zn(II)-induced SF conformational transition. The results indicate that low concentrations of Zn(II) ions promotes the aggregation of SF, while EGCG significantly inhibits the aggregation. Importantly, EGCG can inhibit and even dissociate the Zn(II)-induced beta-sheet aggregation of SF in a dose dependent manner. These findings provide a significant theoretical basis for understanding the effect of Zn(II) and EGCG on the conformational transition of proteins involved in neurodegenerative diseases and developing agents like EGCG as potential treatments.