1r8u
From Proteopedia
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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 with as ligand. 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 Fri Feb 15 16:47:55 2008
