期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
卷 197, 期 -, 页码 68-76出版社
ELSEVIER
DOI: 10.1016/j.ijbiomac.2021.12.072
关键词
3D domain swapping; Amyloid fibrillation; Protein folding
资金
- Ministry of Science and Technology of China [2016YFA0501202]
- National Natural Science Foundation of China [31770797]
The C-terminal domain of M-pro-C can form a 3D domain-swapped dimer and amyloid fibrils under non-denaturing and 3D domain-swappable conditions, respectively. Positive correlations between domain swapping dimerization rates and amyloid fibrillation were found, but not essential, as mutants incapable of 3D domain swapping could still form fibrils. The unpacking of the protofibril core region during 3D domain swapping accelerates the amyloid fibrillation process.
The C-terminal domain of SARS-CoV main protease (M-pro-C) can form 3D domain-swapped dimer by exchanging the alpha(1)-helices fully buried inside the protein hydrophobic core, under non-denaturing conditions. Here, we report that M-pro-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 be-tween the rates of domain swapping dimerization and amyloid fibrillation at different temperatures, and for different mutants. However, some M-pro-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 ex change 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 amyloido-genic 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据