1R8U

NMR structure of CBP TAZ1/CITED2 complex

Summary for 1R8U

• Entry DOI: 10.2210/pdb1r8u/pdb
• NMR Information: BMRB: 5987
• Descriptor: Cbp/p300-interacting transactivator 2, CREB-binding protein, ZINC ION (3 entities in total)
• Functional Keywords: zinc-binding motifs, protein-protein complex, taz zinc finger, transcription-transcription activator complex, transcription/transcription activator
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: Q99967
• Total number of polymer chains: 2
• Total formula weight: 17375.13

Authors

De Guzman, R.N.,Martinez-Yamout, M.,Dyson, H.J.,Wright, P.E. (deposition date: 2003-10-28, release date: 2004-03-23, Last modification date: 2024-05-22)

Primary citation

De Guzman, R.N.,Martinez-Yamout, M.A.,Dyson, H.J.,Wright, P.E.
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.
J.Biol.Chem., 279:3042-3049, 2004

PubMed Abstract: 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.

PubMed: 14594809
DOI: 10.1074/jbc.M310348200

Experimental method

SOLUTION NMR