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  • 标题:Structural basis for recruitment of CBP/p300 by hypoxia-inducible factor-1α
  • 本地全文:下载
  • 作者:Steven J. Freedman ; Zhen-Yu J. Sun ; Florence Poy
  • 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:2002
  • 卷号:99
  • 期号:8
  • 页码:5367-5372
  • DOI:10.1073/pnas.082117899
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:Adaptation to hypoxia is mediated by transactivation of hypoxia-responsive genes by hypoxia-inducible factor-1 (HIF-1) in complex with the CBP and p300 transcriptional coactivators. We report the solution structure of the cysteine/histidine-rich 1 (CH1) domain of p300 bound to the C-terminal transactivation domain of HIF-1. CH1 has a triangular geometry composed of four -helices with three intervening Zn2+-coordinating centers. CH1 serves as a scaffold for folding of the HIF-1 C-terminal transactivation domain, which forms a vise-like clamp on the CH1 domain that is stabilized by extensive hydrophobic and polar interactions. The structure reveals the mechanism of specific recognition of p300 by HIF-1, and shows how HIF-1 transactivation is regulated by asparagine hydroxylation.
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