The N-terminus of TDP-43 promotes its oligomerization and enhances DNA binding affinity

被引：113

作者：

Chang, Chung-ke ^{[1
]}

Wu, Tzong-Huah ^{[2
,3
,4
]}

Wu, Chu-Ya ^{[2
,5
]}

Chiang, Ming-hui ^{[1
]}

Toh, Elsie Khai-Woon ^{[1
]}

Hsu, Yin-Chih ^{[2
]}

Lin, Ku-Feng ^{[2
]}

Liao, Yu-heng ^{[1
]}

Huang, Tai-huang ^{[1
,6
]}

Huang, Joseph Jen-Tse ^{[2
]}

机构：

[1] Acad Sinica, Inst Biomed Sci, Taipei 115, Taiwan

[2] Acad Sinica, Inst Chem, Taipei 115, Taiwan

[3] Acad Sinica, Inst Biochem, Taiwan Int Grad Program, Chem Biol & Mol Biophys Program, Taipei 115, Taiwan

[4] Natl Tsing Hua Univ, Inst Bioinformat & Struct Biol, Hsinchu 300, Taiwan

[5] Natl Taiwan Univ Sci & Technol, Grad Inst Engn, Taipei 106, Taiwan

[6] Natl Taiwan Normal Univ, Dept Phys, Taipei 106, Taiwan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2012年 / 425卷 / 02期

关键词：

TDP-43; DNA/RNA binding; Oligomerization; Neurodegenerative disease; N-terminus; PROTEIN SECONDARY STRUCTURE; SPLICING REGULATION; NMR STRUCTURES; MUTATIONS; RNA; AGGREGATION; FRAGMENTS; INCREASE;

D O I：

10.1016/j.bbrc.2012.07.071

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：219 / 224

页数：6

共 33 条

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