National Center for Magnetic Resonance in Wuhan, Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan, 430071, PR China.
National Center for Magnetic Resonance in Wuhan, Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan, 430071, PR China; University of Chinese Academy of Sciences, Beijing, 100049, PR China.
Biochem Biophys Res Commun. 2020 Nov 19;532(4):655-661. doi: 10.1016/j.bbrc.2020.08.096. Epub 2020 Sep 6.
Cytoplasmic inclusion of TAR DNA-binding protein 43 (TDP-43) is a hallmark of most ALS (amyotrophic lateral sclerosis) and FTLD (Frontotemporal dementia), yet the aggregation of TDP-43 remains unclear. In this study, we proved the existence of amyloid-like structures of C-terminal domain of TDP-43 (TDP-C) in bacterial inclusion bodies (IBs), and obtained a homogenous fibril sample by seeding from the components of aggregated TDP-C in Escherichiacoli IBs. The results from solid-state NMR spectroscopy suggest that the homogenous fibrils were seeded from a tiny amount of aggregated TDP-C compositions in IBs; the structure characteristics of the rigid fibril core are identified of β-rich structures, and show subtle relativity with the hydrophobicity of residues. Our study here provides a further understanding of TDP-43 protein aggregation and fibrillation.
细胞质内包含 TAR DNA 结合蛋白 43（TDP-43）是大多数肌萎缩性侧索硬化症（ALS）和额颞叶痴呆（FTLD）的标志，但 TDP-43 的聚集仍然不清楚。在这项研究中，我们证明了 TDP-43（TDP-C）的 C 末端结构域的淀粉样样结构的存在于细菌包含体（IBs）中，并通过从大肠杆菌 IBs 中聚集的 TDP-C 的成分中进行接种获得了均匀的纤维样品。固态 NMR 光谱的结果表明，均匀的纤维是由 IBs 中聚集的少量 TDP-C 成分接种而来的；刚性纤维核心的结构特征被鉴定为富含β结构，并与残基的疏水性显示出细微的相关性。我们的研究进一步了解了 TDP-43 蛋白的聚集和纤维化。
