TDP-43 低复杂度结构域的多面性：液滴和淀粉样纤维的形成。
The Different Faces of the TDP-43 Low-Complexity Domain: The Formation of Liquid Droplets and Amyloid Fibrils.
机构信息
Institute of Chemistry, Academia Sinica, Nangang, Taipei City 115, Taiwan.
Department of Chemistry, National Taiwan University, Taipei City 115, Taiwan.
出版信息
Int J Mol Sci. 2021 Jul 30;22(15):8213. doi: 10.3390/ijms22158213.
Transactive response DNA-binding protein 43 (TDP-43) is a nucleic acid-binding protein that is involved in transcription and translation regulation, non-coding RNA processing, and stress granule assembly. Aside from its multiple functions, it is also known as the signature protein in the hallmark inclusions of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) patients. TDP-43 is built of four domains, but its low-complexity domain (LCD) has become an intense research focus that brings to light its possible role in TDP-43 functions and involvement in the pathogenesis of these neurodegenerative diseases. Recent endeavors have further uncovered the distinct biophysical properties of TDP-43 under various circumstances. In this review, we summarize the multiple structural and biochemical properties of LCD in either promoting the liquid droplets or inducing fibrillar aggregates. We also revisit the roles of the LCD in paraspeckles, stress granules, and cytoplasmic inclusions to date.
反式作用响应 DNA 结合蛋白 43（TDP-43）是一种核酸结合蛋白，参与转录和翻译调控、非编码 RNA 加工以及应激颗粒组装。除了具有多种功能外，它还是肌萎缩侧索硬化症（ALS）和额颞叶变性（FTLD）患者标志性特征包涵体中的标志性蛋白。TDP-43 由四个结构域组成，但它的低复杂度结构域（LCD）成为了一个研究热点，揭示了它在 TDP-43 功能中的可能作用以及在这些神经退行性疾病发病机制中的作用。最近的研究进一步揭示了 TDP-43 在各种情况下的独特生物物理特性。在这篇综述中，我们总结了 LCD 在促进液滴或诱导纤维状聚集方面的多种结构和生化特性。我们还回顾了 LCD 在核周斑点、应激颗粒和细胞质包涵体中的作用。
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