1p4q: Difference between revisions

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[[Image:1p4q.jpg|left|200px]]
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{{STRUCTURE_1p4q|  PDB=1p4q  |  SCENE=  }}  
{{STRUCTURE_1p4q|  PDB=1p4q  |  SCENE=  }}  


'''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===




==Overview==
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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.
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{{ABSTRACT_PUBMED_12778114}}


==About this Structure==
==About this Structure==
1P4Q is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P4Q OCA].  
1P4Q is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P4Q OCA].  


==Reference==
==Reference==
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[[Category: Helix]]
[[Category: Helix]]
[[Category: Protein-protein complex]]
[[Category: Protein-protein complex]]
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Revision as of 03:42, 28 July 2008

File:1p4q.png

Template:STRUCTURE 1p4q

Solution structure of the CITED2 transactivation domain in complex with the p300 CH1 domain

Template:ABSTRACT PUBMED 12778114

About this Structure

1P4Q is a Protein complex structure of sequences from Homo sapiens. Full experimental 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

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