1GWR

HUMAN OESTROGEN RECEPTOR ALPHA LIGAND-BINDING DOMAIN IN COMPLEX WITH 17BETA-OESTRADIOL AND TIF2 NRBOX3 PEPTIDE

1GWR の概要

• エントリーDOI: 10.2210/pdb1gwr/pdb
• 関連するPDBエントリー: 1A52 1AKF 1ERE 1ERR 1G50 1GWQ 1HCP 1HCQ 1QKT 1QKU 3ERD 3ERT
• 分子名称: OESTROGEN RECEPTOR, TRANSCRIPTION INTERMEDIARY FACTOR-2, ESTRADIOL, ... (4 entities in total)
• 機能のキーワード: nuclear receptor, transcription factor, transactivation, agonist, af2 coactivator, receptor, activator, transcripti regulation, dna-binding, nuclear protein, zinc finger, ster binding, phosphorylation, polymorphism, alternative splicing
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• 細胞内の位置: Isoform 1: Nucleus. Isoform 3: Nucleus: P03372; Nucleus: Q15596
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 58771.40

構造登録者

Pike, A.C.W.,Brzozowski, A.M. (登録日: 2002-03-22, 公開日: 2002-08-29, 最終更新日: 2023-12-13)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.4 Å)