5JJM

Crystal Structure of Homodimeric Androgen Receptor Ligand-Binding Domain bound to DHT and LxxLL peptide

5JJM の概要

• エントリーDOI: 10.2210/pdb5jjm/pdb
• 分子名称: Androgen receptor, SULFATE ION, TRIETHYLENE GLYCOL, ... (13 entities in total)
• 機能のキーワード: nuclear receptor, transcription factor, oxosteroid receptor, human androgen receptor, transcription
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Nucleus : P10275 P10275
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 125816.63

構造登録者

Estebanez-Perpina, E.,Fuentes-Prior, P. (登録日: 2016-04-24, 公開日: 2017-03-15, 最終更新日: 2024-10-09)

主引用文献

Nadal, M.,Prekovic, S.,Gallastegui, N.,Helsen, C.,Abella, M.,Zielinska, K.,Gay, M.,Vilaseca, M.,Taules, M.,Houtsmuller, A.B.,van Royen, M.E.,Claessens, F.,Fuentes-Prior, P.,Estebanez-Perpina, E.
Structure of the homodimeric androgen receptor ligand-binding domain.
Nat Commun, 8:14388-14388, 2017

PubMed Abstract: The androgen receptor (AR) plays a crucial role in normal physiology, development and metabolism as well as in the aetiology and treatment of diverse pathologies such as androgen insensitivity syndromes (AIS), male infertility and prostate cancer (PCa). Here we show that dimerization of AR ligand-binding domain (LBD) is induced by receptor agonists but not by antagonists. The 2.15-Å crystal structure of homodimeric, agonist- and coactivator peptide-bound AR-LBD unveils a 1,000-Å large dimerization surface, which harbours over 40 previously unexplained AIS- and PCa-associated point mutations. An AIS mutation in the self-association interface (P767A) disrupts dimer formation in vivo, and has a detrimental effect on the transactivating properties of full-length AR, despite retained hormone-binding capacity. The conservation of essential residues suggests that the unveiled dimerization mechanism might be shared by other nuclear receptors. Our work defines AR-LBD homodimerization as an essential step in the proper functioning of this important transcription factor.

PubMed: 28165461
DOI: 10.1038/ncomms14388

実験手法

X-RAY DIFFRACTION (2.15 Å)