(-)-Epigallocatechin-3-gallate Directly Binds Cyclophilin D: A Potential Mechanism for Mitochondrial Protection

(1) Background: (-)-Epigallocatechin-3-gallate (EGCG) has been reported to improve mitochondrial function in cell models, while the underlying mechanism is not clear. Cyclophilin D (CypD) is a key protein that regulates mitochondrial permeability transition pore (mPTP) opening. (2) Methods: In this...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2022-12, Vol.27 (24), p.8661
Main Authors: Wu, Annan, Zhang, Jie, Li, Quanhong, Liao, Xiaojun, Wang, Chunyu, Zhao, Jing
Format: Article
Language:English
Subjects:
Amino acids
Analysis
Binding sites
Care and treatment
Cell culture
CypD
Diagnosis
EGCG
Electrostatic properties
Energy
Epigallocatechin gallate
Green tea
Health aspects
interaction
Membrane permeability
Mitochondria - metabolism
Mitochondrial diseases
Mitochondrial Membrane Transport Proteins - metabolism
Mitochondrial permeability transition pore
Molecular docking
Molecular Docking Simulation
Molecular dynamics
mPTP
NMR
Nuclear magnetic resonance
Nutritional aspects
Oxidative phosphorylation
Peptidyl-Prolyl Isomerase F - metabolism
Permeability
Proteins
Resonance
Sensors
Simulation
Software
Statistical analysis
Surface plasmon resonance
Titration
Variance analysis
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Summary:(1) Background: (-)-Epigallocatechin-3-gallate (EGCG) has been reported to improve mitochondrial function in cell models, while the underlying mechanism is not clear. Cyclophilin D (CypD) is a key protein that regulates mitochondrial permeability transition pore (mPTP) opening. (2) Methods: In this study, we found that EGCG directly binds to CypD and this interaction was investigated by surface plasmon resonance (SPR), nuclear magnetic resonance (NMR) and molecular dynamic (MD) simulation. (3) Results: SPR showed an affinity of 2.7 × 10 M. The binding sites of EGCG on CypD were mapped to three regions by 2D NMR titration, which are Region 1 (E23-V29), Region 2 (T89-G104) and Region 3 (G124-I133). Molecular docking showed binding interface consistent with 2D NMR titration. MD simulations revealed that at least two conformations of EGCG-CypD complex exist, one with E23, D27, L90 and V93 as the most contributed residues and E23, L5 and I133 for the other. The major driven force for EGCG-CypD binding are Van der Waals and electrostatic interactions. (4) Conclusions: These results provide the structural basis for EGCG-CypD interaction, which might be a potential mechanism of how EGCG protects mitochondrial functions.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules27248661