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  • 标题:Structural characterization of the ternary complex that mediates termination of NF-κB signaling by IκBα
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  • 作者:Sulakshana P. Mukherjee ; Pedro O. Quintas ; Reginald McNulty
  • 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:2016
  • 卷号:113
  • 期号:22
  • 页码:6212-6217
  • DOI:10.1073/pnas.1603488113
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:The transcription factor NF-κB is used in many systems for the transduction of extracellular signals into the expression of signal-responsive genes. Published structural data explain the activation of NF-κB through degradation of its dedicated inhibitor IκBα, but the mechanism by which NF-κB–mediated signaling is turned off by its removal from the DNA in the presence of newly synthesized IκBα (termed stripping) is unknown. Previous kinetic studies showed that IκBα accelerates NF-κB dissociation from DNA, and a transient ternary complex between NF-κB, its cognate DNA sequence, and IκBα was observed. Here we structurally characterize the >100-kDa ternary complex by NMR and negative stain EM and show a modeled structure that is consistent with the measurements. These data provide a structural basis for previously unidentified insights into the molecular mechanism of stripping.
  • 关键词:transcriptional activation ; NMR ; negative stain electron microscopy ; protein–DNA complex ; protein–protein complex
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