The N-terminus of TDP-43 promotes its oligomerization and enhances DNA binding affinity
The N-terminus of TDP-43 promotes its oligomerization and enhances DNA binding affinity
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DOI：
10.1016/j.bbrc.2012.07.071
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发表时间：
2012-08-24
影响因子：
3.1
通讯作者：
Huang, Joseph Jen-Tse
中科院分区：
文献类型：
--
作者：
Chang, Chung-ke;Wu, Tzong-Huah;Huang, Joseph Jen-Tse
TDP-43 是一种 DNA/RNA 结合蛋白，与肌萎缩侧索硬化症 (ALS) 和额颞叶变性 (FTLD-U) 等不同的神经退行性疾病相关。在此，通过核磁共振 (NMR)、圆二色性 (CD) 和荧光各向异性研究的结合，仔细表征了 TDP-43 N 末端的结构和物理性质。我们首次证明了 N 末端在促进 TDP-43 寡聚化和增强其 DNA 结合亲和力方面的重要性。还公开了 N 末端的未鉴定结构域。我们的研究结果提供了对 TDP-43 N 端结构域功能的深入了解。 (c) 2012 Elsevier Inc. 保留所有权利。
TDP-43 is a DNA/RNA-binding protein associated with different neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-U). Here, the structural and physical properties of the N-terminus on TDP-43 have been carefully characterized through a combination of nuclear magnetic resonance (NMR), circular dichroism (CD) and fluorescence anisotropy studies. We demonstrate for the first time the importance of the N-terminus in promoting TDP-43 oligomerization and enhancing its DNA-binding affinity. An unidentified structural domain in the N-terminus is also disclosed. Our findings provide insights into the N-terminal domain function of TDP-43. (c) 2012 Elsevier Inc. All rights reserved.