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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.

SUBMITTER: Freedman SJ

PROVIDER: S-EPMC122775 | biostudies-literature | 2002 Apr

REPOSITORIES: biostudies-literature

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

Freedman Steven J SJ Sun Zhen-Yu J ZY Poy Florence F Kung Andrew L AL Livingston David M DM Wagner Gerhard G Eck Michael J MJ

Proceedings of the National Academy of Sciences of the United States of America 20020401 8

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 ...[more]

PMID: 11959990

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