Abstract:
: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 alpha. CH1 has a triangular geometry composed of four alpha-helices with three intervening Zn(2+)-coordinating centers. CH1 serves as a scaffold for folding of the HIF-1 alpha 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 alpha, and shows how HIF-1 alpha transactivation is regulated by asparagine hydroxylation.
journal_name
Proc Natl Acad Sci U S Aauthors
Freedman SJ,Sun ZY,Poy F,Kung AL,Livingston DM,Wagner G,Eck MJdoi
10.1073/pnas.082117899keywords:
subject
Has Abstractpub_date
2002-04-16 00:00:00pages
5367-72issue
8eissn
0027-8424issn
1091-6490pii
99/8/5367journal_volume
99pub_type
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