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  • 标题:Redox-mediated regulation of an evolutionarily conserved cross-β structure formed by the TDP43 low complexity domain
  • 本地全文:下载
  • 作者:Yi Lin ; Xiaoming Zhou ; Masato Kato
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2020
  • 卷号:117
  • 期号:46
  • 页码:28727-28734
  • DOI:10.1073/pnas.2012216117
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:A methionine-rich low complexity (LC) domain is found within a C-terminal region of the TDP43 RNA-binding protein. Self-association of this domain leads to the formation of labile cross-β polymers and liquid-like droplets. Treatment with H 2 O 2 caused phenomena of methionine oxidation and droplet melting that were reversed upon exposure of the oxidized protein to methionine sulfoxide reductase enzymes. Morphological features of the cross-β polymers were revealed by H 2 O 2 -mediated footprinting. Equivalent TDP43 LC domain footprints were observed in polymerized hydrogels, liquid-like droplets, and living cells. The ability of H 2 O 2 to impede cross-β polymerization was abrogated by the prominent M337V amyotrophic lateral sclerosis-causing mutation. These observations may offer insight into the biological role of TDP43 in facilitating synapse-localized translation as well as aberrant aggregation of the protein in neurodegenerative diseases.
  • 关键词:low-complexity sequence ; cross-beta polymers ; TDP-43 ; redox sensor ; neurodegenerative disorders
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