A team led by researchers of the Institute of Biomedicine of the University of Barcelona (IBUB) –at the Barcelona Science Park– and the Research Institute of the Hospital de la Santa Creu i Sant Pau (IIB-Sant Pau) shows for the first time, the three-dimensional structure of the homodimeric androgen receptor ligand-binding domain, a structure that eluded researchers for years. This new structure of the nuclear receptor allows explaining more than forty mutations related to prostate cancer, one of the most common worldwide and especially in Catalonia, as well as known developing disorders.

The research has been co-directed by Eva Estébanez Perpiñá, IBUB researcher and Serra Hunter professor, together with Pablo Fuentes Prior researcher from IBB-Sant Pau, both members of the Research Group Bases Estructurals de Processos Fisiopatològics Fonamentals, recognized by the Generalitat de Catalunya, and from the Xarxa Nacional de Receptors Nuclears (National Network of Nuclear Receptors) from the Ministry of Economy, Industry and Competitiveness. 

The human androgen receptor is a key protein in the regular development and activity of the prostate in response to male hormones such as testosterone. The deregulating activity of the receptor is directly related to the carcinogenesis of the prostate gland. Therefore, “the resolution of its three-dimensional structure is an essential key to diagnose and predict prostate cancer, as well as monitoring patient’s resistance to medicine”, says Eva Estébanez Perpiñá.

The androgenic receptor was and still is the central target of the fight against prostate cancer. Identifying its homodimeric three-dimensional structure suggests new therapeutic strategies. “Actually, we started exploring the design of a new generation of drugs in collaboration with pharmaceutical companies in order to step forward towards a precision medicine for the prostate cancer”, says Estébanez Perpiñá. 

This work, published in Nature Communications, enables understanding the molecular bases of mutations detected in patients of prostate cancer and also in the ones with androgenic insensitivity syndrome (AIS), a disease caused by the mutations in the X chromosome that create a resistance to male hormones.

The research, signed by Marta Nadal (IBUB) as its first co-author, counts with the participation of Marta Taulés, researcher of the Scientific and Technological Centers of of the University of Barcelona (CCiTUB), and the team of Marta Vilaseca, researcher of the Institute for Research in Biomedicine (IRB Barcelona) –both centers located at the Barcelona Science Park (PCB)– apart from two researchers from the team of Professor Franck Claessens (Univesity of Leuven, Belgium) and the researchers Adriaan Houtsmuller and Martin van Royen (Erasmus University Rotterdam, Netherlands). 

• Article reference:   

M. Nadal, S. Prekovic, N. Gallastegui, C. Helsen, M. Abella, K. Zielinska, M. Gay, M. Vilaseca, M. Taulés, A. B. Houtsmuller, M. E. van Royen, F. Claessens, P. Fuentes Prior, i E. Estébanez Perpiñá, «Three-dimensional Structure of the Homodimeric Androgen Receptor Ligand-Binding Domain». Nature Communications, 6 de febrer de 2017. Doi: 10.1038/ncomms14388