The N-terminal dimerization is required for TDP-43 splicing activity
Jiang, LL; Xue, W; Hong, JY; Zhang, JT; Li, MJ; Yu, SN; He, JH; Hu, HY
2017
发表期刊SCIENTIFIC REPORTS
ISSN2045-2322
卷号7期号:-页码:-
文章类型期刊论文
摘要TDP-43 is a nuclear factor that functions in promoting pre-mRNA splicing. Deletion of the N-terminal domain (NTD) and nuclear localization signal (NLS) (i.e., TDP-35) results in mislocalization to cytoplasm and formation of inclusions. However, how the NTD functions in TDP-43 activity and proteinopathy remains largely unknown. Here, we studied the structure and function of the NTD in inclusion formation and pre-mRNA splicing of TDP-43 by using biochemical and biophysical approaches. We found that TDP-43 NTD forms a homodimer in solution in a concentration-dependent manner, and formation of intermolecular disulfide results in further tetramerization. Based on the NMR structure of TDP-43 NTD, the dimerization interface centered on Leu71 and Val72 around the beta 7-strand was defined by mutagenesis and size-exclusion chromatography. Cell experiments revealed that the N-terminal dimerization plays roles in protecting TDP-43 against formation of cytoplasmic inclusions and enhancing pre-mRNA splicing activity of TDP-43 in nucleus. This study may provide mechanistic insights into the physiological function of TDP-43 and its related proteinopathies.
关键词Amyotrophic-lateral-sclerosis Dna-binding Protein Frontotemporal Lobar Degeneration Nuclear Factor Tdp-43 Structural Determinants Inclusion Formation Fibril Formation Cellular-model Acid Binding Cftr Exon-9
DOI10.1038/s41598-017-06263-3
关键词[WOS]AMYOTROPHIC-LATERAL-SCLEROSIS ; DNA-BINDING PROTEIN ; FRONTOTEMPORAL LOBAR DEGENERATION ; NUCLEAR FACTOR TDP-43 ; STRUCTURAL DETERMINANTS ; INCLUSION FORMATION ; FIBRIL FORMATION ; CELLULAR-MODEL ; ACID BINDING ; CFTR EXON-9
收录类别SCI
语种英语
WOS记录号WOS:000406285700103
引用统计
被引频次:9[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.sinap.ac.cn/handle/331007/28867
专题中科院上海应用物理研究所2011-2018年
推荐引用方式
GB/T 7714
Jiang, LL,Xue, W,Hong, JY,et al. The N-terminal dimerization is required for TDP-43 splicing activity[J]. SCIENTIFIC REPORTS,2017,7(-):-.
APA Jiang, LL.,Xue, W.,Hong, JY.,Zhang, JT.,Li, MJ.,...&Hu, HY.(2017).The N-terminal dimerization is required for TDP-43 splicing activity.SCIENTIFIC REPORTS,7(-),-.
MLA Jiang, LL,et al."The N-terminal dimerization is required for TDP-43 splicing activity".SCIENTIFIC REPORTS 7.-(2017):-.
条目包含的文件 下载所有文件
文件名称/大小 文献类型 版本类型 开放类型 使用许可
The N-terminal dimer(3528KB)期刊论文作者接受稿开放获取CC BY-NC-SA浏览 下载
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Jiang, LL]的文章
[Xue, W]的文章
[Hong, JY]的文章
百度学术
百度学术中相似的文章
[Jiang, LL]的文章
[Xue, W]的文章
[Hong, JY]的文章
必应学术
必应学术中相似的文章
[Jiang, LL]的文章
[Xue, W]的文章
[Hong, JY]的文章
相关权益政策
暂无数据
收藏/分享
文件名: The N-terminal dimerization is required for TDP-43 splicing activity.pdf
格式: Adobe PDF
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。