1GWQ

HUMAN OESTROGEN RECEPTOR ALPHA LIGAND-BINDING DOMAIN IN COMPLEX WITH RALOXIFENE CORE AND TIF2 NRBOX2 PEPTIDE

Summary for 1GWQ

• Entry DOI: 10.2210/pdb1gwq/pdb
• Related: 1A52 1AKF 1ERE 1ERR 1G50 1GWQ 1HCP 1HCQ 1QKT 1QKU 3ERD 3ERT
• Descriptor: OESTROGEN RECEPTOR, NUCLEAR RECEPTOR COACTIVATOR 2, RALOXIFENE CORE, ... (4 entities in total)
• Functional Keywords: nuclear receptor, transcription factor, transactivation, agonist, af2 coactivator, receptor, activator, transcripti regulation, dna-binding, nuclear protein, zinc finger, ster binding, phosphorylation, polymorphism, alternative splicin
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 4
• Total formula weight: 59498.20

Authors

Pike, A.C.W.,Brzozowski, A.M. (deposition date: 2002-03-22, release date: 2002-08-29, Last modification date: 2023-12-13)

Primary citation

Warnmark, A.,Treuter, E.,Gustafsson, J.-A.,Hubbard, R.E.,Brzozowski, A.M.,Pike, A.C.W.
Interaction of Transcriptional Intermediary Factor 2 Nuclear Receptor Box Peptides with the Coactivator Binding Site of Estrogen Receptor Alpha.
J.Biol.Chem., 277:21862-, 2002

PubMed Abstract: The activation function 2/ligand-dependent interaction between nuclear receptors and their coregulators is mediated by a short consensus motif, the so-called nuclear receptor (NR) box. Nuclear receptors exhibit distinct preferences for such motifs depending both on the bound ligand and on the NR box sequence. To better understand the structural basis of motif recognition, we characterized the interaction between estrogen receptor alpha and the NR box regions of the p160 coactivator TIF2. We have determined the crystal structures of complexes between the ligand-binding domain of estrogen receptor alpha and 12-mer peptides from the Box B2 and Box B3 regions of TIF2. Surprisingly, the Box B3 module displays an unexpected binding mode that is distinct from the canonical LXXLL interaction observed in other ligand-binding domain/NR box crystal structures. The peptide is shifted along the coactivator binding site in such a way that the interaction motif becomes LXXYL rather than the classical LXXLL. However, analysis of the binding properties of wild type NR box peptides, as well as mutant peptides designed to probe the Box B3 orientation, suggests that the Box B3 peptide primarily adopts the "classical" LXXLL orientation in solution. These results highlight the potential difficulties in interpretation of protein-protein interactions based on co-crystal structures using short peptide motifs.

PubMed: 11937504
DOI: 10.1074/JBC.M200764200

Experimental method

X-RAY DIFFRACTION (2.45 Å)