1p4q
From Proteopedia
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|PDB= 1p4q |SIZE=350|CAPTION= <scene name='initialview01'>1p4q</scene> | |PDB= 1p4q |SIZE=350|CAPTION= <scene name='initialview01'>1p4q</scene> | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=ZN:ZINC ION'>ZN</scene> | + | |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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|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]) | |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]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1l3e|1L3E]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1p4q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p4q OCA], [http://www.ebi.ac.uk/pdbsum/1p4q PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1p4q RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Colorectal cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602700 602700]], Rubinstein-Taybi syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602700 602700]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Sun, Z-Y J.]] | [[Category: Sun, Z-Y J.]] | ||
[[Category: Wagner, G.]] | [[Category: Wagner, G.]] | ||
| - | [[Category: ZN]] | ||
[[Category: helix]] | [[Category: helix]] | ||
[[Category: protein-protein complex]] | [[Category: protein-protein complex]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:54:52 2008'' |
Revision as of 19:54, 30 March 2008
| |||||||
| Ligands: | |||||||
| Gene: | CITED2 OR MRG1 (Homo sapiens), EP300 OR P300 (Homo sapiens) | ||||||
| Activity: | Histone acetyltransferase, with EC number 2.3.1.48 | ||||||
| Related: | 1L3E
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| 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.
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 Sun Mar 30 22:54:52 2008
