Structural Biology of Human Nuclear Receptors

Department of Biochemistry
and molecular Biology
University of Barcelona

Molecular Physiology Laboratory

Carrer Baldiri Reixac 15-21
08028 Barcelona, Spain
office +34 93 403 11 19
lab +34 93 403 11 81


Principal investigator: Eva Estébanez-Perpiñá PostDoc researcher: Marta Nadal PhD students: Alba Jiménez Lab Manager and Technician: Montserrat Abella

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Our laboratory studies several members of the family of nuclear receptors (NRs) that regulate gene expression in many tissues. There are 48 nuclear receptors in humans, some of them have their ligand and functions well characterized, while others are regarded as orphans as their ligand or function is still not completely described. Among the steroid subclass of NRs, we study the androgen receptor (AR), which is implicated in prostate cancer, androgen insensitivity syndromes and the neurodegenerative Kennedy’s disease. AR is therefore a crucial therapeutical target. We propase a structure-based drug design strategy that combines our structural in formation obtained by X-ray crystallography, combinatorial chemistry, and bioinformatics to identify alternative ways to treat prostate cancer by targeting alternative sites on the AR surface.

The laboratory is also interested in the characterization of several orphan receptors with therapeutical potential as drug targets. We aim to visualize several NRs and the ir key protein and ligand interactions to understand their function in the cell under physiological or pathological conditions. We tack le the biological processes we study from a multidisciplinary approach using several biochemical and biophysical techniques.

Nuclear Receptors Structure and Function

Crucial to our work is the usage of protein crystallography/X-ray diffraction and other biophys ical approaches to visualize the atomic de t ai ls of NR structure and their key ligand and protein interactions.

Androgen Receptor Structure-Function and Drug Discovery

  • Study the role of androgen receptor’s regulatory surfaces AF-2 (Coactivator Binding) and BF-3 (Binding Function 3) pockets in its transcriptional activity.
  • Allosteric modulators of AR func ti on as therapeutic drugs to treat prostate cancer using the molecular insights gained from X-ray crysta llography and SPR.
  • Computational studies on androgen receptor regula tory surfaces. Unravel the relationship between AR regulatory surfaces, their conformational dynamics and biological functions.
  • ldentification and validation of biological protein partners of t he BF-3 pocket.
  • Elucidation of the molecular determinants underlying the neuromuscular neurode


Structure of the homodimeric androgen receptor ligand-binding domain. Nadal M, Prekovic S, Gallastegui N, Helsen C, Abella M, Zielinska K, Gay M, Vilaseca M, Taulès M, Houtsmuller AB, van Royen ME, Claessens F, Fuentes-Prior P, Estébanez-Perpiñá E. Nat Commun. 2017 Feb 6;8:14388.

Diversity of Quaternary Structures Regulates Nuclear Receptor Activities. Fuentes-Prior P, Rojas A, Hagler AT, Estébanez-Perpiñá E. Trends Biochem Sci. 2019 Jan;44(1):2-6.

Advances in our structural understanding of orphan nuclear receptors. Gallastegui N, Mackinnon JA, Fletterick RJ, Estébanez-Perpiñá E. Trends Biochem Sci. 2015 Jan;40(1):25-35.

Allosteric conversation in the androgen receptor ligand-binding domain surfaces. Grosdidier S, Carbó LR, Buzón V, Brooke G, Nguyen P, Baxter JD, Bevan C, Webb P, Fernández-Recio J, Estébanez-Perpiñá E. Mol Endocrinol. 2012 Jul;26(7):1078-90.

The oncoprotein BCL11A binds to orphan nuclear receptor TLX and potentiates its transrepressive function. Estruch SB, Buzón V, Carbó LR, Schorova L, Lüders J, Estébanez-Perpiñá E. PLoS One. 2012;7(6):e37963.


Immunomodulatory effects of diclofenac in leukotyces throug the targeting of Kv1.3 voltage-dependent potassium channels


P. Fuentes-Prior, A. Rojas, AT Hagler, E. Estébanez-Perpiñá


2018 Oct 4, in press

Groups IBUB

Impact of KCNE subunits on KCNQ1 (Kv7.1) channel membrane surface targeting


P. Fuentes-Prior, A. Rojas, AT Hagler, E. Estébanez-Perpiñá


2019 Gen 6