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.
