The aggregation process of peptides and proteins is of great relevance as it is associated with a wide range of highly debilitating disorders, including Alzheimer's and Parkinson's diseases. The natural product (-)-epigallocatechin-3-gallate (EGCG) can redirect this process away from amyloid fibrils and towards non-toxic oligomers. In this study we used nuclear magnetic resonance (NMR) spectroscopy to characterize the binding of EGCG to a set of natively structured and unstructured proteins. The results show that the binding process is dramatically dependent on the conformational properties of the protein involved, as EGCG interacts with different binding modes depending on the folding state of the protein. We used replica exchange molecular dynamics simulations to reproduce the trends observed in the NMR experiments, and analyzed the resulting samplings to identify the dominant direct interactions between EGCG and ordered and disordered proteins.

Molecular determinants of the interaction of EGCG with ordered and disordered proteins / Fusco, G.; Sanz-Hernandez, M.; Ruggeri, F. S.; Vendruscolo, M.; Dobson, C. M.; De Simone, A.. - In: BIOPOLYMERS. - ISSN 0006-3525. - 109:10(2018), p. e23117. [10.1002/bip.23117]

Molecular determinants of the interaction of EGCG with ordered and disordered proteins

De Simone A.
2018

Abstract

The aggregation process of peptides and proteins is of great relevance as it is associated with a wide range of highly debilitating disorders, including Alzheimer's and Parkinson's diseases. The natural product (-)-epigallocatechin-3-gallate (EGCG) can redirect this process away from amyloid fibrils and towards non-toxic oligomers. In this study we used nuclear magnetic resonance (NMR) spectroscopy to characterize the binding of EGCG to a set of natively structured and unstructured proteins. The results show that the binding process is dramatically dependent on the conformational properties of the protein involved, as EGCG interacts with different binding modes depending on the folding state of the protein. We used replica exchange molecular dynamics simulations to reproduce the trends observed in the NMR experiments, and analyzed the resulting samplings to identify the dominant direct interactions between EGCG and ordered and disordered proteins.
2018
Molecular determinants of the interaction of EGCG with ordered and disordered proteins / Fusco, G.; Sanz-Hernandez, M.; Ruggeri, F. S.; Vendruscolo, M.; Dobson, C. M.; De Simone, A.. - In: BIOPOLYMERS. - ISSN 0006-3525. - 109:10(2018), p. e23117. [10.1002/bip.23117]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/828849
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