Is amyloid fibrillation related to 3D domain swapping for the C-terminal domain of SARS-CoV main protease?
| Autor: | Zhiliang Yuan, Zhi Qu, Bo Duan, Tianyi Wang, Jiajun Xu, Bin Xia |
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| Rok vydání: | 2021 |
| Předmět: |
Models
Molecular Protein Conformation alpha-Helical Amyloid Protein Folding NMR Nuclear magnetic resonance MD Molecular dynamics animal structures macromolecular substances Molecular Dynamics Simulation RMSF Root mean square fluctuation Biochemistry Article Polymerization Protein Domains Structural Biology Disulfides Molecular Biology Coronavirus 3C Proteases SASA Solvent accessible surface area SEC Size-exclusion chromatography 3D domain swapping Amyloid fibrillation fungi Temperature General Medicine Amyloidosis Recombinant Proteins Kinetics CD Circular dichroism Mutation Dimerization Mpro-C C-terminal domain of SARS-CoV main protease |
| Zdroj: | International Journal of Biological Macromolecules |
| ISSN: | 1879-0003 |
| Popis: | The C-terminal domain of SARS-CoV main protease (Mpro-C) can form 3D domain-swapped dimer by exchanging the α1-helices fully buried inside the protein hydrophobic core, under non-denaturing conditions. Here, we report that Mpro-C can also form amyloid fibrils under the 3D domain-swappable conditions in vitro, and the fibrils are not formed through runaway/propagated domain swapping. It is found that there are positive correlations between the rates of domain swapping dimerization and amyloid fibrillation at different temperatures, and for different mutants. However, some Mpro-C mutants incapable of 3D domain swapping can still form amyloid fibrils, indicating that 3D domain swapping is not essential for amyloid fibrillation. Furthermore, NMR H/D exchange data and molecular dynamics simulation results suggest that the protofibril core region tends to unpack at the early stage of 3D domain swapping, so that the amyloid fibrillation can proceed during the 3D domain swapping process. We propose that 3D domain swapping makes it possible for the unpacking of the amyloidogenic fragment of the protein and thus accelerates the amyloid fibrillation process kinetically, which explains the well-documented correlations between amyloid fibrillation and 3D domain swapping observed in many proteins. |
| Databáze: | OpenAIRE |
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