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  • 标题:Transiently structured head domains control intermediate filament assembly
  • 本地全文:下载
  • 作者:Xiaoming Zhou ; Yi Lin ; 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:2021
  • 卷号:118
  • 期号:8
  • 页码:1
  • DOI:10.1073/pnas.2022121118
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:Low complexity (LC) head domains 92 and 108 residues in length are, respectively, required for assembly of neurofilament light (NFL) and desmin intermediate filaments (IFs). As studied in isolation, these IF head domains interconvert between states of conformational disorder and labile, β-strand–enriched polymers. Solid-state NMR (ss-NMR) spectroscopic studies of NFL and desmin head domain polymers reveal spectral patterns consistent with structural order. A combination of intein chemistry and segmental isotope labeling allowed preparation of fully assembled NFL and desmin IFs that could also be studied by ss-NMR. Assembled IFs revealed spectra overlapping with those observed for β-strand–enriched polymers formed from the isolated NFL and desmin head domains. Phosphorylation and disease-causing mutations reciprocally alter NFL and desmin head domain self-association yet commonly impede IF assembly. These observations show how facultative structural assembly of LC domains via labile, β-strand–enriched self-interactions may broadly influence cell morphology.
  • 关键词:low complexity domains ; intermediate filaments ; phase separation ; labile cross-β structures ; in situ structural analysis
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