Structural Transformation of the Amyloidogenic Core Region of TDP-43 Protein Initiates Its Aggregation and Cytoplasmic Inclusion
文献类型：期刊论文
| 作者 | Jiang, Lei-Lei ; Che, Mei-Xia ; Zhao, Jian ; Zhou, Chen-Jie ; Xie, Mu-Yun ; Li, Hai-Yin ; He, Jian-Hua ; Hu, Hong-Yu |
| 刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
 |
| 出版日期 | 2013 |
| 卷号 | 288期号:27页码:CONCATENATE(Sheet1!I321,-Sheet1!J321) |
| ISSN号 | 0021-9258 |
| 英文摘要 | TDP-43 (TAR DNA-binding protein of 43 kDa) is a major deposited protein in amyotrophic lateral sclerosis and frontotemporal dementia with ubiquitin. A great number of genetic mutations identified in the flexible C-terminal region are associated with disease pathologies. We investigated the molecular determinants of TDP-43 aggregation and its underlying mechanisms. We identified a hydrophobic patch (residues 318-343) as the amyloidogenic core essential for TDP-43 aggregation. Biophysical studies demonstrated that the homologous peptide formed a helix-turn-helix structure in solution, whereas it underwent structural transformation from an alpha-helix to a beta-sheet during aggregation. Mutation or deletion of this core region significantly reduced the aggregation and cytoplasmic inclusions of full-length TDP-43 (or TDP-35 fragment) in cells. Thus, structural transformation of the amyloidogenic core initiates the aggregation and cytoplasmic inclusion formation of TDP-43. This particular core region provides a potential therapeutic target to design small-molecule compounds for mitigating TDP-43 proteinopathies. |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000321515800027 |
| 公开日期 | 2014-06-13 |
| 源URL | [http://ir.sinap.ac.cn/handle/331007/13920]  |
| 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, Lei-Lei,Che, Mei-Xia,Zhao, Jian,et al. Structural Transformation of the Amyloidogenic Core Region of TDP-43 Protein Initiates Its Aggregation and Cytoplasmic Inclusion[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2013,288(27):CONCATENATE(Sheet1!I321,-Sheet1!J321). |
| APA | Jiang, Lei-Lei.,Che, Mei-Xia.,Zhao, Jian.,Zhou, Chen-Jie.,Xie, Mu-Yun.,...&Hu, Hong-Yu.(2013).Structural Transformation of the Amyloidogenic Core Region of TDP-43 Protein Initiates Its Aggregation and Cytoplasmic Inclusion.JOURNAL OF BIOLOGICAL CHEMISTRY,288(27),CONCATENATE(Sheet1!I321,-Sheet1!J321). |
| MLA | Jiang, Lei-Lei,et al."Structural Transformation of the Amyloidogenic Core Region of TDP-43 Protein Initiates Its Aggregation and Cytoplasmic Inclusion".JOURNAL OF BIOLOGICAL CHEMISTRY 288.27(2013):CONCATENATE(Sheet1!I321,-Sheet1!J321). |
入库方式： OAI收割
来源：上海应用物理研究所
浏览0
下载0
收藏0
其他版本
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。