CAS OpenIR  > 中科院上海应用物理研究所2011-2019年
Structural Transformation of the Amyloidogenic Core Region of TDP-43 Protein Initiates Its Aggregation and Cytoplasmic Inclusion
Jiang, Lei-Lei; Che, Mei-Xia; Zhao, Jian; Zhou, Chen-Jie; Xie, Mu-Yun; Li, Hai-Yin; He, Jian-Hua; Hu, Hong-Yu
2013
Source PublicationJOURNAL OF BIOLOGICAL CHEMISTRY
ISSN0021-9258
Volume288Issue:27Pages:CONCATENATE(Sheet1!I321,-Sheet1!J321)
AbstractTDP-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.
Indexed BySCI
Language英语
Funding Project应物所项目组
WOS IDWOS:000321515800027
Citation statistics
Cited Times:54[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.sinap.ac.cn/handle/331007/13920
Collection中科院上海应用物理研究所2011-2019年
Recommended Citation
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).
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