1p4q
From Proteopedia
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'''Solution structure of the CITED2 transactivation domain in complex with the p300 CH1 domain''' | '''Solution structure of the CITED2 transactivation domain in complex with the p300 CH1 domain''' | ||
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[[Category: Sun, Z-Y J.]] | [[Category: Sun, Z-Y J.]] | ||
[[Category: Wagner, G.]] | [[Category: Wagner, G.]] | ||
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| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 04:41:08 2008'' | |
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Revision as of 01:41, 3 May 2008
Solution structure of the CITED2 transactivation domain in complex with the p300 CH1 domain
Overview
Expression of hypoxia-responsive genes is mediated by the heterodimeric transcription factor hypoxia-inducible factor-1 (HIF-1) in complex with the p300/CREB-binding protein (p300/CBP) transcriptional coactivator. The protein CITED2, which binds p300/CBP, is thought to be a negative regulator of HIF-1 transactivation. We show that the CITED2 transactivation domain (TAD) disrupts a complex of the HIF-1alpha C-terminal TAD (C-TAD) and the cysteine-histidine-rich 1 (CH1) domain of p300/CBP by binding CH1 with high affinity. The high-resolution solution structure of the CITED2 TAD-p300 CH1 complex shows that the CITED2 TAD, like the HIF-1alpha C-TAD, folds on a helical, Zn2+-containing CH1 scaffold. The CITED2 TAD binds a different, more extensive surface of CH1 than does the HIF-1alpha C-TAD. However, a conserved 'LPXL' sequence motif in CITED2 and HIF-1alpha interacts with an overlapping binding site on CH1. Mutation of the LPEL sequence in full-length CITED2 abolishes p300 binding in vivo. These findings reveal that CITED2 regulates HIF-1 by competing for a hot spot on the p300 CH1 domain.
About this Structure
1P4Q is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural basis for negative regulation of hypoxia-inducible factor-1alpha by CITED2., Freedman SJ, Sun ZY, Kung AL, France DS, Wagner G, Eck MJ, Nat Struct Biol. 2003 Jul;10(7):504-12. PMID:12778114 Page seeded by OCA on Sat May 3 04:41:08 2008
