title: Advances in our structural understanding of orphan nuclear receptors.
abstract: Nuclear receptors (NRs) are key players in the regulation of gene expression, coordinating protein assemblies upon their surfaces. NRs are regulated by ligand binding, which remodels the interaction surfaces and subsequently influences macromolecular complex formation. Structural biology has been instrumental in the discovery of some of these ligands, but there are still orphan NRs (ONRs) whose bona fide ligands have yet to be identified. Over the past decade, fundamental structural and functional breakthroughs have led to a deeper understanding of ONR actions and their multidomain organization. Here, we summarize the structural advances in ONRs with implications for the therapeutic treatment of diseases such as metabolic syndrome and cancer.
authors.affiliation: The Institute of Biomedicine of the University of Barcelona (IBUB), Department of Biochemistry and Molecular Biology, University of Barcelona (UB), Baldiri Reixac 15-21, 08028 Barcelona, Spain.
authors.forename: Nerea
authors.initials: N
authors.lastname: Gallastegui
authors.affiliation: The Institute of Biomedicine of the University of Barcelona (IBUB), Department of Biochemistry and Molecular Biology, University of Barcelona (UB), Baldiri Reixac 15-21, 08028 Barcelona, Spain.
authors.forename: Jonathan A G
authors.initials: JA
authors.lastname: Mackinnon
authors.affiliation: The Department of Biochemistry and Biophysics, University of California San Francisco (UCSF), San Francisco, CA, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fletterick
authors.affiliation: The Institute of Biomedicine of the University of Barcelona (IBUB), Department of Biochemistry and Molecular Biology, University of Barcelona (UB), Baldiri Reixac 15-21, 08028 Barcelona, Spain. Electronic address: evaestebanez@ub.edu.
authors.forename: Eva
authors.initials: E
authors.lastname: Estébanez-Perpiñá
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D057093:Orphan Nuclear Receptors / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D015398:Signal Transduction; D013329:Structure-Activity Relationship
chemical_list: D004268:DNA-Binding Proteins; D008024:Ligands; D057093:Orphan Nuclear Receptors
keywords: deorphanization; full-length; ligands; orphan nuclear receptors; structure–function relations