1r8u
From Proteopedia
| Line 4: | Line 4: | ||
|PDB= 1r8u |SIZE=350|CAPTION= <scene name='initialview01'>1r8u</scene> | |PDB= 1r8u |SIZE=350|CAPTION= <scene name='initialview01'>1r8u</scene> | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=ZN:ZINC ION'>ZN</scene> | + | |LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= CITED2, MRG1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= CITED2, MRG1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1r8u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1r8u OCA], [http://www.ebi.ac.uk/pdbsum/1r8u PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1r8u RCSB]</span> | ||
}} | }} | ||
| Line 27: | Line 30: | ||
[[Category: Martinez-Yamout, M.]] | [[Category: Martinez-Yamout, M.]] | ||
[[Category: Wright, P E.]] | [[Category: Wright, P E.]] | ||
| - | [[Category: ZN]] | ||
[[Category: protein-protein complex]] | [[Category: protein-protein complex]] | ||
[[Category: taz zinc finger]] | [[Category: taz zinc finger]] | ||
[[Category: zinc-binding motif]] | [[Category: zinc-binding motif]] | ||
| - | ''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 23:24:52 2008'' |
Revision as of 20:24, 30 March 2008
| |||||||
| Ligands: | |||||||
| Gene: | CITED2, MRG1 (Homo sapiens) | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| 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
Page seeded by OCA on Sun Mar 30 23:24:52 2008
