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Molecular determinants of the interaction of EGCG with ordered and disordered proteins
Author(s) -
Fusco Giuliana,
SanzHernandez Maximo,
Ruggeri Francesco S.,
Vendruscolo Michele,
Dobson Christopher M.,
De Simone Alfonso
Publication year - 2018
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.23117
Subject(s) - chemistry , nuclear magnetic resonance spectroscopy , folding (dsp implementation) , molecular dynamics , intrinsically disordered proteins , biophysics , epigallocatechin gallate , protein folding , heteronuclear single quantum coherence spectroscopy , two dimensional nuclear magnetic resonance spectroscopy , plasma protein binding , crystallography , biochemistry , computational chemistry , stereochemistry , polyphenol , electrical engineering , biology , antioxidant , engineering
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.