Molecular mechanism of oxidation-induced TDP-43 RRM1 aggregation and loss of function

Chung Ke Chang, Ming Hui Chiang, Elsie Khai Woon Toh, Chi Fon Chang, Tai Huang Huang*

*此作品的通信作者

研究成果: 雜誌貢獻期刊論文同行評審

44 引文 斯高帕斯(Scopus)

摘要

Cysteine oxidation of the two RNA recognition motifs (RRM1 and RRM2) of TDP-43, a multi-domain protein involved in neurodegenerative diseases, results in loss of function and accumulation of insoluble aggregates under both in vitro and in vivo conditions. However, the molecular mechanisms linking cysteine oxidation to protein aggregation and functional aberration remain unknown. We report that oxidation of cysteines in RRM1, but not in other domains, induced conformational changes which subsequently resulted in protein aggregation and loss of nucleic acid-binding activity. Thus, oxidation-induced conformational change of RRM1 plays a key role in TDP-43 aggregation and disease progression. Structured summary of protein interactions: RRM2 and RRM2 bind by molecular sieving (View Interaction: 1, 2, 3, 4) RRM1 and RRM1 bind by comigration in sds page (View Interaction: 1, 2, 3) RRM1 and RRM1 bind by classical fluorescence spectroscopy (View interaction) RRM2 and RRM2 bind by molecular sieving (View Interaction: 1, 2).

原文英語
頁(從 - 到)575-582
頁數8
期刊FEBS Letters
587
發行號6
DOIs
出版狀態已發佈 - 2013 3月 18

ASJC Scopus subject areas

  • 生物物理學
  • 結構生物學
  • 生物化學
  • 分子生物學
  • 遺傳學
  • 細胞生物學

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