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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Current Research

Our laboratory studies several members of the superfamily of nuclear receptors (NRs), which are transcription factors that regulate gene expression. There are 48 nuclear receptors in humans, some of them have their endogenous ligand and functions well characterized, while others are regarded as orphans as their ligand or function is still not completely understood.

We primarily focus on the androgen receptor (AR), glucocorticoid receptor (GR) and human tailless (NR2E1/TLX) receptor. AR is implicated in prostate cancer, androgen insensitivity syndromes and the rare neurodegenerative Kennedy’s disease. AR is also the central drug target to fight prostate cancer using antiandrogens. GR is an essential receptor for life and binds glucocorticoids, one of the most important drug classes to treat immune diseases and inflammation (asthma, psoriasis, arthritis). We study GR oligomerization to further understand its monomer to dimer to tetramer transitions and pharmacological outcome of glucocorticoids. Lastly, we focus on TLX for its therapeutic potential as drug target to treat glioblastoma and meduloblastoma as well as modulation of brain neurogenesis.


Nuclear Receptors Structure and Function Relationship

We tackle the biological processes controlled by NRs from a multidisciplinary approach using several biochemical and biophysical techniques (X-ray crystallography, SPR, SAXS, MS) as well as in vitro and in cellulo to understand their function in tissues under (patho)-physiological conditions.

AR, GR and TLX in Drug Discovery

  • We combine structure-based drug design, combinatorial chemistry, and bioinformatics to identify novel first-in-class AR precision drugs against prostate cancer and other AR-related diseases.
  • Our studies on GR oligomerization focuses on the development of novel glucocorticoids devoid of severe side effects that modulate GR multimers on chromatin.
  • Design of TLX modulators to tackle incurable brain tumors.


Jiménez-Panizo A, Alegre-Martí A, Tettey TT, Fettweis G, Abella M, Antón R, Johnson TA, Kim S, Schiltz RL, Núñez-Barrios I, Font-Díaz J, Caelles C, Valledor AF, Pérez P, Rojas AM, Fernández-Recio J, Presman DM, Hager GL, Fuentes-Prior P, Estébanez-Perpiñá E. The multivalency of the glucocorticoid receptor ligand-binding domain explains its manifold physiological activities, Nucleic Acids Research, 2022; gkac1119,

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. Structure of the homodimeric androgen receptor ligand-binding domain. Nature Communications, 2017 Feb 6;8:14388.

Kandel P, Semerci F, Mishra R, Choi W, Bajic A, Baluya D, Ma L, Chen K, Cao AC, Phongmekhin T, Matinyan N, Jiménez-Panizo A, Chamakuri S, Raji IO, Chang L, Fuentes-Prior P, MacKenzie KR, Benn CL, Estébanez-Perpiñá E, Venken K, Moore DD, Young DW, Maletic-Savatic M. Oleic acid is an endogenous ligand of TLX/NR2E1 that triggers hippocampal neurogenesis. Proc Natl Acad Sci U S A, 2022 Mar 29; 119(13): e2023784119.

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

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


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