1T5Z

Crystal Structure of the Androgen Receptor Ligand Binding Domain (LBD) with DHT and a peptide derived from its physiological coactivator ARA70

1T5Z の概要

• エントリーDOI: 10.2210/pdb1t5z/pdb
• 関連するPDBエントリー: 1T63 1T65
• 分子名称: Androgen receptor, Nuclear receptor coactivator 4, 5-ALPHA-DIHYDROTESTOSTERONE, ... (4 entities in total)
• 機能のキーワード: androgen receptor ligand binding domain ara70 crystal structure coactivators, hormone-growth factor complex, hormone/growth factor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus: P10275
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 31460.90

構造登録者

Estebanez-Perpina, E.,Moore, J.M.R.,Mar, E.,Nguyen, P.,Delgado-Rodrigues, E.,Baxter, J.D.,Webb, P.,Fletterick, R.J.,Guy, R.K. (登録日: 2004-05-05, 公開日: 2005-01-25, 最終更新日: 2024-02-14)

主引用文献

Estebanez-Perpina, E.,Moore, J.M.R.,Mar, E.,Delgado-Rodrigues, E.,Nguyen, P.,Baxter, J.D.,Buehrer, B.M.,Webb, P.,Fletterick, R.J.,Guy, R.K.
The Molecular Mechanisms of Coactivator Utilization in Ligand-dependent Transactivation by the Androgen Receptor.
J.Biol.Chem., 280:8060-8068, 2005

PubMed Abstract: Androgens drive sex differentiation, bone and muscle development, and promote growth of hormone-dependent cancers by binding the nuclear androgen receptor (AR), which recruits coactivators to responsive genes. Most nuclear receptors recruit steroid receptor coactivators (SRCs) to their ligand binding domain (LBD) using a leucine-rich motif (LXXLL). AR is believed to recruit unique coactivators to its LBD using an aromatic-rich motif (FXXLF) while recruiting SRCs to its N-terminal domain (NTD) through an alternate mechanism. Here, we report that the AR-LBD interacts with both FXXLF motifs and a subset of LXXLL motifs and that contacts with these LXXLL motifs are both necessary and sufficient for SRC-mediated AR regulation of transcription. Crystal structures of the activated AR in complex with both recruitment motifs reveal that side chains unique to the AR-LBD rearrange to bind either the bulky FXXLF motifs or the more compact LXXLL motifs and that AR utilizes subsidiary contacts with LXXLL flanking sequences to discriminate between LXXLL motifs.

PubMed: 15563469
DOI: 10.1074/jbc.M407046200

実験手法

X-RAY DIFFRACTION (2.3 Å)