1QKU

WILD TYPE ESTROGEN NUCLEAR RECEPTOR LIGAND BINDING DOMAIN COMPLEXED WITH ESTRADIOL

1QKU の概要

• エントリーDOI: 10.2210/pdb1qku/pdb
• 関連するPDBエントリー: 1A52 1AKF 1ERE 1ERR 1HCP 1HCQ 1QKM 1QKN 1QKU 3ERD 3ERT
• 分子名称: ESTRADIOL RECEPTOR, ESTRADIOL (3 entities in total)
• 機能のキーワード: nuclear receptor, agonism, antagonism, estradiol receptor, steroid, structural proteomics in europe, spine, structural genomics
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Isoform 1: Nucleus . Isoform 3: Nucleus. Nucleus: P03372
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 86676.33

構造登録者

Ruff, M.,Gangloff, M.,Eiler, S.,Duclaud, S.,Wurtz, J.M.,Moras, D. (登録日: 1999-08-05, 公開日: 2000-08-18, 最終更新日: 2024-05-08)

主引用文献

Gangloff, M.,Ruff, M.,Eiler, S.,Duclaud, S.,Wurtz, J.M.,Moras, D.
Crystal structure of a mutant hERalpha ligand-binding domain reveals key structural features for the mechanism of partial agonism.
J. Biol. Chem., 276:15059-15065, 2001

PubMed Abstract: The crystal structure of a triple cysteine to serine mutant ERalpha ligand-binding domain (LBD), complexed with estradiol, shows that despite the presence of a tightly bound agonist ligand, the protein exhibits an antagonist-like conformation, similar to that observed in raloxifen and 4-hydroxytamoxifen-bound structures. This mutated receptor binds estradiol with wild type affinity and displays transcriptional activity upon estradiol stimulation, but with limited potency (about 50%). This partial activity is efficiently repressed in antagonist competition assays. The comparison with available LBD structures reveals key features governing the positioning of helix H12 and highlights the importance of cysteine residues in promoting an active conformation. Furthermore the present study reveals a hydrogen bond network connecting ligand binding to protein trans conformation. These observations support a dynamic view of H12 positioning, where the control of the equilibrium between two stable locations determines the partial agonist character of a given ligand.

PubMed: 11278577
DOI: 10.1074/jbc.M009870200

実験手法

X-RAY DIFFRACTION (3.2 Å)