Structural basis for recruitment of CBP/p300 by hypoxia-inducible factor-1 alpha.

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.

authors

Freedman SJ,Sun ZY,Poy F,Kung AL,Livingston DM,Wagner G,Eck MJ

doi

10.1073/pnas.082117899

keywords:

subject

Has Abstract

pub_date

2002-04-16 00:00:00

pages

5367-72

issue

8

eissn

0027-8424

issn

1091-6490

pii

99/8/5367

journal_volume

99

pub_type

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