1p4q: Difference between revisions
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[[Image:1p4q.jpg|left|200px]]< | [[Image:1p4q.jpg|left|200px]] | ||
'''Solution structure of the CITED2 transactivation domain in complex with the p300 CH1 domain''' | {{Structure | ||
|PDB= 1p4q |SIZE=350|CAPTION= <scene name='initialview01'>1p4q</scene> | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=ZN:ZINC ION'>ZN</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Histone_acetyltransferase Histone acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.48 2.3.1.48] | |||
|GENE= CITED2 OR MRG1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), EP300 OR P300 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |||
}} | |||
'''Solution structure of the CITED2 transactivation domain in complex with the p300 CH1 domain''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1P4Q is a [ | 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]. | ||
==Reference== | ==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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/12778114 12778114] | ||
[[Category: Histone acetyltransferase]] | [[Category: Histone acetyltransferase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: protein-protein complex]] | [[Category: protein-protein complex]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:19:59 2008'' | ||
Revision as of 11:20, 20 March 2008
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| 1p4q | |||||||||||||
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| Ligands: | ZN | ||||||||||||
| Gene: | CITED2 OR MRG1 (Homo sapiens), EP300 OR P300 (Homo sapiens) | ||||||||||||
| Activity: | Histone acetyltransferase, with EC number 2.3.1.48 | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
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.
Disease
Known diseases associated with this structure: Colorectal cancer OMIM:[602700], Rubinstein-Taybi syndrome OMIM:[602700]
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
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