The Flexible, Extended Coil of the PDZ-Binding Motif of the Three Deadly Human Coronavirus E Proteins Plays a Role in Pathogenicity
Abstract
:1. Introduction
2. Materials and Methods
2.1. Molecular Modelling
Template Selection, Model Construction, and Quality Assessment
2.2. High Ambiguity Driven DOCKing (HADDOCK): Molecular Docking
2.3. Interaction Analysis: PyMol and Protein-Ligand Interaction Profiler (PLiP)
2.4. Molecular Dynamic (MD) Simulations of the hCoV E Proteins in POPC Lipid Bilayer
2.5. Trajectory Analysis, Principal Component Analysis (PCA), and Lipid Bilayer Analysis
3. Results
3.1. Homology Modelling and Quality Assessment
3.1.1. More Virulent hCoVs: SARS-CoV-1, -2, and MERS-CoV
3.1.2. Less Virulent hCoVs: HCoV-229E and HCoV-NL63
3.2. Molecular Docking and Interaction Analysis
3.3. Molecular Dynamics Simulation Analysis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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HCoVs | Hydrophobic | Hydrogen | Ionic | π-Cation | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
P266 | T270 | V271 | R272 | V284 | V314 | F318 | L321 | L267 | G268 | A269 | T270 | V271 | S281 | R272 | R282 | R272 | |
7NTK (8-mer) | none | L74 | V75 | V70 | L74 | L73 P71 | L73 V75 | V75 | V75 | V75 | V75 (×2) | none | L73 (×2) D72 | D72 | D72 | none | none |
SARS-CoV-1 | V76 (×2) | none | L75 | L74 | none | none | L75 (×2) P72 | L75 | V76 | V76 | V76 | none | L75 | none | D73 | none | none |
SARS-CoV-2 | none | L74 | V75 | none | L74 | L73 (×2) | L73 | V75 | V75 | V75 | V75 (×2) | D72 | L73 (×2) | D72 | none | D72 | none |
MERS-CoV | V82 | W81 | none | none | none | P77 E80 | E80 V82 | V82 | V82 | V82 | V82 | none | E80 (×2) | D79 (×2) | D79 | none | none |
HCoV-229E | F77 | I75 | none | F70 | none | none | F77 | F77 | F77 | F77 | F77 | none | none | none | none | none | F70 |
HCoV-NL63 | V77 | none | none | none | V77 | none | V74 L75 | none | V77 | V77 | V77 | none | N76 | none | none | none | none |
HCoVs | Hydrophobic | Hydrogen | Ionic | π-Stacking | ||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
P266 | L267 | T270 | V271 | R272 | V284 | V314 | F318 | L321 | P266 | L267 | G268 | A269 | T270 | V271 | R272 | S281 | N315 | R272 | E274 | R282 | F318 | |
7NTK (8-mer) | none | none | L74 | V75 | V70 | L74 | L73 P71 | L73 V75 | V75 | none | V75 | V75 | V75 (×2) | none | L73 (×2) D72 | none | D72 | none | D72 | none | none | none |
SARS-CoV-1 | E69 (×2) | none | L74 | none | none | none | L75 | V76 | none | S68 | E69 | E69 | E69 | none | L75 | none | none | none | none | none | D73 | none |
SARS-CoV-2 | none | none | L74 | V75 | none | none | L73 | L73 V75 | V75 | none | V75 | V75 | V75 (×2) | D72 | L73 (×2) | none | D72 | none | D72 | R61 | none | none |
MERS-CoV | V82 | none | none | none | none | none | none | V82 | none | none | V82 | V82 | V82 | none | E80 | P78 | none | none | none | none | none | W81 |
HCoV-229E | F77 | F77 (×2) | V74 | none | none | none | Y61 (×2) | F77 (×2) | F77 | none | F77 | F77 | F77 | none | Y61 | none | none | I60 Y61 Q62 | none | none | none | Y61 |
HCoV-NL63 | none | none | none | none | none | none | none | E73 V74 V77 | V77 | none | N76 | N76 | N76 | none | V77 | none | none | none | none | none | none | Y61 |
HCoV E Protein System | Area per Lipid (nm2) | Bilayer Thickness (nm) | Lateral Diffusion Coefficient (cm2/s) | Hydrogen Bonds |
---|---|---|---|---|
SARS-CoV-1 | 0.64 ± 0.01 | 4.39 ± 2.87 | 0.37 ± 0.02 | 10.58 |
SARS-CoV-2 | 0.64 ± 0.01 | 4.25 ± 2.48 | 0.43 ± 0.09 | 13.04 |
MERS-CoV | 0.66 ± 0.01 | 5.78 ± 3.37 | 0.84 ± 0.01 | 9.22 |
HCoV-229E | 0.65 ± 0.01 | 4.65 ± 2.71 | 0.46 ± 0.02 | 11.89 |
HCoV-NL63 | 0.65 ± 0.01 | 4.46 ± 2.60 | 0.34 ± 0.05 | 12.64 |
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Schoeman, D.; Cloete, R.; Fielding, B.C. The Flexible, Extended Coil of the PDZ-Binding Motif of the Three Deadly Human Coronavirus E Proteins Plays a Role in Pathogenicity. Viruses 2022, 14, 1707. https://doi.org/10.3390/v14081707
Schoeman D, Cloete R, Fielding BC. The Flexible, Extended Coil of the PDZ-Binding Motif of the Three Deadly Human Coronavirus E Proteins Plays a Role in Pathogenicity. Viruses. 2022; 14(8):1707. https://doi.org/10.3390/v14081707
Chicago/Turabian StyleSchoeman, Dewald, Ruben Cloete, and Burtram C. Fielding. 2022. "The Flexible, Extended Coil of the PDZ-Binding Motif of the Three Deadly Human Coronavirus E Proteins Plays a Role in Pathogenicity" Viruses 14, no. 8: 1707. https://doi.org/10.3390/v14081707