News

20.02.2017

Publication of "Structure of the homodimeric androgen receptor ligand-binding domain"

PhD. Marta Taulès, technician from Analysis of Molecular Interactions Technology of CCiTUB, has participated as a co-author on the publication of the article "Structure of the homodimeric androgen receptor ligand-binding domain" in the journal Nature Communications, which was released on February 6th 2017.

This international study was led by researchers from the Institute of Biomedicine of the University of Barcelona (IBUB) and the Research Institute of the Hospital de Sant Pau (IIB-Sant Pau). The research also involved researchers from the Catholic University of Leuven, Belgium and from Erasmus University Rotterdam, Netherland).

In this publication we can see the first three-dimensional structure of the dimer binding domain androgenic hormones in the human androgen receptor. This study allows us to understand the molecular basis of mutations detected in individuals suffering from prostate cancer, and also in those who suffer androgen insensitivity syndrome (AIS).

According to statements by one of the researchers, Pablo Fuentes Prior, from this discovery "new drugs can be developed, rather than compete with the binding of natural hormones, as do antiandrogens current, they block the pathophysiological processes resulting from the union of these hormones".

For more information:

Nature Communications: [+]
Universitat de Barcelona: [+]

Abstract of the article:

“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.”