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http://hdl.handle.net/2445/108258
Title: | Structure of the Homodimeric androgen receptor ligand-binding domain |
Author: | Nadal, Marta Prekovic, Stefan Gallastegui, Nerea Helsen, Christine Abella, Montserrat Zielinska, Karolina Gay, Marina Vilaseca, Marta Taulés i Marín, Marta Houtsmuller, Adriaan B. van Royen, Martin E. Claessens, Frank Fuentes-Prior, Pablo Estébanez Perpiñá, Eva |
Keywords: | Receptors d'hormones Difracció de raigs X Radiocristal·lografia Hormone receptors X-rays diffraction X-ray crystallography |
Issue Date: | 6-Feb-2017 |
Publisher: | Nature Publishing Group |
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-Å2 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/ncomms14388 |
It is part of: | Nature Communications, 2017, vol. 8, p. 14388-14398 |
URI: | http://hdl.handle.net/2445/108258 |
Related resource: | https://doi.org/10.1038/ncomms14388 |
ISSN: | 2041-1723 |
Appears in Collections: | Articles publicats en revistes (Bioquímica i Biomedicina Molecular) |
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