The N-terminal dimerization is required for TDP-43 splicing activity
文献类型：期刊论文
| 作者 | Jiang, LL; Xue, W; Hong, JY; Zhang, JT; Li, MJ; Yu, SN; He, JH; Hu, HY |
| 刊名 | SCIENTIFIC REPORTS
 |
| 出版日期 | 2017 |
| 卷号 | 7期号:-页码:- |
| ISSN号 | 2045-2322 |
| 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 |
| DOI | 10.1038/s41598-017-06263-3 |
| 文献子类 | 期刊论文 |
| 英文摘要 | 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. |
| WOS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 |
| 语种 | 英语 |
| WOS记录号 | WOS:000406285700103 |
| 源URL | [http://ir.sinap.ac.cn/handle/331007/28867]  |
| 专题 | 上海应用物理研究所_中科院上海应用物理研究所2011-2017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):-. |
入库方式： OAI收割
来源：上海应用物理研究所
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