Structural basis for recruitment of CBP/p300 by hypoxia-inducible factor-1 alpha.
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.
Mesh Terms:
Amino Acid Sequence, Animals, Asparagine, Escherichia coli, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Magnetic Resonance Spectroscopy, Models, Molecular, Molecular Sequence Data, Nuclear Proteins, Protein Binding, Protein Conformation, Protein Folding, Protein Structure, Secondary, Protein Structure, Tertiary, Sequence Homology, Amino Acid, Trans-Activators, Transcription Factors, Transcriptional Activation, Zinc
Amino Acid Sequence, Animals, Asparagine, Escherichia coli, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Magnetic Resonance Spectroscopy, Models, Molecular, Molecular Sequence Data, Nuclear Proteins, Protein Binding, Protein Conformation, Protein Folding, Protein Structure, Secondary, Protein Structure, Tertiary, Sequence Homology, Amino Acid, Trans-Activators, Transcription Factors, Transcriptional Activation, Zinc
Proc. Natl. Acad. Sci. U.S.A.
Date: Apr. 16, 2002
PubMed ID: 11959990
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