1r8u
From Proteopedia
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| - | [[Image:1r8u.jpg|left|200px]] | + | [[Image:1r8u.jpg|left|200px]] |
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| - | '''NMR structure of CBP TAZ1/CITED2 complex''' | + | {{Structure |
| + | |PDB= 1r8u |SIZE=350|CAPTION= <scene name='initialview01'>1r8u</scene> | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=ZN:ZINC ION'>ZN</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= CITED2, MRG1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''NMR structure of CBP TAZ1/CITED2 complex''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1R8U is a [ | + | 1R8U is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R8U OCA]. |
==Reference== | ==Reference== | ||
| - | Interaction of the TAZ1 domain of the CREB-binding protein with the activation domain of CITED2: regulation by competition between intrinsically unstructured ligands for non-identical binding sites., De Guzman RN, Martinez-Yamout MA, Dyson HJ, Wright PE, J Biol Chem. 2004 Jan 23;279(4):3042-9. Epub 2003 Oct 31. PMID:[http:// | + | Interaction of the TAZ1 domain of the CREB-binding protein with the activation domain of CITED2: regulation by competition between intrinsically unstructured ligands for non-identical binding sites., De Guzman RN, Martinez-Yamout MA, Dyson HJ, Wright PE, J Biol Chem. 2004 Jan 23;279(4):3042-9. Epub 2003 Oct 31. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14594809 14594809] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
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[[Category: protein-protein complex]] | [[Category: protein-protein complex]] | ||
[[Category: taz zinc finger]] | [[Category: taz zinc finger]] | ||
| - | [[Category: zinc-binding | + | [[Category: zinc-binding motif]] |
| - | ''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 13:48:25 2008'' |
Revision as of 11:48, 20 March 2008
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| Ligands: | |||||||
| Gene: | CITED2, MRG1 (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
NMR structure of CBP TAZ1/CITED2 complex
Overview
The TAZ1 domain of the homologous transcriptional coactivators CREB-binding protein (CBP) and p300 forms a complex with CITED2 (CBP/p300-interacting transactivator with ED-rich tail), inhibiting the activity of the hypoxia inducible factor (HIF-1alpha) and thereby attenuating the cellular response to low tissue oxygen concentration. We report the NMR structure of the CBP TAZ1 domain bound to the activation domain of CIT-ED2. The structure of TAZ1, consisting of four alpha-helices (alpha(1)-alpha(4)) stabilized by three zinc atoms, is very similar in the CITED2 and HIF-1alpha complexes. The activation domain of CITED2 is unstructured when free and folds upon binding, forming a helix (termed alpha(A)) and an extended structure that wraps around TAZ1. The CITED2 alpha(A) helix packs in the TAZ1 alpha(1)/alpha(4) interface, a site that forms weak interactions with the poorly defined aminoterminal alpha-helix of HIF-1alpha. CITED2 and HIF-1alpha both contain a four residue motif, LP(E/Q)L, which binds in the TAZ1 alpha(1)/alpha(2)/alpha(3) junction in each complex. The carboxyl-terminal region of CITED2 forms an extended structure with hydrophobic contacts in the TAZ1 alpha(1)/alpha(3) interface in the site occupied by the HIF-1alpha alpha(B) helix. CITED2 does not bind at all to the TAZ1 site occupied by the HIF-1alpha carboxyl-terminal helix. The HIF-1alpha and CITED2 domains utilize partly overlapping surfaces of TAZ1 to achieve high affinity binding and to compete effectively with each other for interaction with CBP/p300; CITED2 and HIF-1alpha use these binding sites differently to maintain similar binding affinities in order to displace each other in a feedback loop during the hypoxic response.
About this Structure
1R8U is a Protein complex structure of sequences from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA.
Reference
Interaction of the TAZ1 domain of the CREB-binding protein with the activation domain of CITED2: regulation by competition between intrinsically unstructured ligands for non-identical binding sites., De Guzman RN, Martinez-Yamout MA, Dyson HJ, Wright PE, J Biol Chem. 2004 Jan 23;279(4):3042-9. Epub 2003 Oct 31. PMID:14594809
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