5JJM

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

Summary for 5JJM

• Entry DOI: 10.2210/pdb5jjm/pdb
• Descriptor: Androgen receptor, SULFATE ION, TRIETHYLENE GLYCOL, ... (13 entities in total)
• Functional Keywords: nuclear receptor, transcription factor, oxosteroid receptor, human androgen receptor, transcription
• Biological source: Homo sapiens (Human); More
• Cellular location: Nucleus : P10275 P10275
• Total number of polymer chains: 12
• Total formula weight: 125816.63

Authors

Estebanez-Perpina, E.,Fuentes-Prior, P. (deposition date: 2016-04-24, release date: 2017-03-15, Last modification date: 2024-10-09)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.15 Å)