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

Giuliana Fusco; Maximo Sanz-Hernandez; Francesco S. Ruggeri; Michele Vendruscolo; Christopher M. Dobson; Alfonso De Simone

doi:10.1002/bip.23117

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

Giuliana Fusco, Maximo Sanz-Hernandez, Francesco S. Ruggeri, Michele Vendruscolo, Christopher M. Dobson, Alfonso De Simone^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

24 Citations (Scopus)

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.

Original language	English
Article number	e23117
Journal	Biopolymers
Volume	109
Issue number	10
DOIs	https://doi.org/10.1002/bip.23117
Publication status	Published - Aug 2018
Externally published	Yes

Access to Document

10.1002/bip.23117

Cite this

@article{f0094e5e95fb4de6a69edad32ec8b948,

title = "Molecular determinants of the interaction of EGCG with ordered and disordered proteins",

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.",

author = "Giuliana Fusco and Maximo Sanz-Hernandez and Ruggeri, {Francesco S.} and Michele Vendruscolo and Dobson, {Christopher M.} and {De Simone}, Alfonso",

note = "Publisher Copyright: {\textcopyright} 2018 Wiley Periodicals, Inc.",

year = "2018",

month = aug,

doi = "10.1002/bip.23117",

language = "English",

volume = "109",

journal = "Biopolymers",

issn = "0006-3525",

publisher = "Wiley",

number = "10",

}

TY - JOUR

T1 - Molecular determinants of the interaction of EGCG with ordered and disordered proteins

AU - Fusco, Giuliana

AU - Sanz-Hernandez, Maximo

AU - Ruggeri, Francesco S.

AU - Vendruscolo, Michele

AU - Dobson, Christopher M.

AU - De Simone, Alfonso

PY - 2018/8

Y1 - 2018/8

N2 - 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.

AB - 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.

U2 - 10.1002/bip.23117

DO - 10.1002/bip.23117

M3 - Article

C2 - 29603125

AN - SCOPUS:85044680751

VL - 109

JO - Biopolymers

JF - Biopolymers

SN - 0006-3525

IS - 10

M1 - e23117

ER -

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

Abstract

Access to Document

Fingerprint

Cite this