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, LL; Che, MX; Zhao, J; Zhou, CJ; Xie, MY; Li, HY; He, JH; Hu, HY |
| 刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
 |
| 出版日期 | 2013 |
| 卷号 | 288期号:27页码:19614-19624 |
| 通讯作者 | Hu, HY (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai 200031, Peoples R China.,hyhu@sibcb.ac.cn |
| 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. |
| 学科主题 | Biochemistry & Molecular Biology |
| 类目[WOS] | Biochemistry & Molecular Biology |
| 关键词[WOS] | AMYOTROPHIC-LATERAL-SCLEROSIS ; FRONTOTEMPORAL LOBAR DEGENERATION ; ALZHEIMERS A-BETA-42 PEPTIDE ; HUMAN ALPHA-SYNUCLEIN ; FIBRIL FORMATION ; SPLICING REGULATION ; TERMINAL FRAGMENTS ; RNA DEPLETION ; HUMAN-DISEASE ; MUTATIONS |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000321515800027 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/470]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Jiang, LL,Che, MX,Zhao, J,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):19614-19624. |
| APA | Jiang, LL.,Che, MX.,Zhao, J.,Zhou, CJ.,Xie, MY.,...&Hu, HY.(2013).Structural Transformation of the Amyloidogenic Core Region of TDP-43 Protein Initiates Its Aggregation and Cytoplasmic Inclusion.JOURNAL OF BIOLOGICAL CHEMISTRY,288(27),19614-19624. |
| MLA | Jiang, LL,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):19614-19624. |
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