title: Nuclear receptor full-length architectures: confronting myth and illusion with high resolution.
abstract: The crystal structures of three nuclear receptor (NR) complexes have emerged to reveal their multidomain architectures on DNA. These pictures provide unprecedented views of interfacial couplings between the DNA-binding domains (DBDs) and ligand-binding domains (LBDs). The detailed pictures contrast with previous interpretations of low-resolution electron microscopy (EM) and small angle X-ray scattering (SAXS) data, which had suggested a common architecture with noninteracting DBDs and LBDs. Revisiting both historical and recent interpretations of NR architecture, we invoke new principles underlying higher-order quaternary organization and the allosteric transmission of signals between domains. We also discuss how NR architectures are being probed in living cells to understand dimerization and DNA-binding events in real time.
authors.affiliation: Sanford-Burnham Medical Research Institute, Metabolic Disease Program, 6400 Sanger Road, Lake Nona, FL 32827, USA. Electronic address: frastinejad@sanfordburnham.org.
authors.forename: Fraydoon
authors.initials: F
authors.lastname: Rastinejad
authors.affiliation: INRA, UMR866 Dynamique Musculaire et Métabolisme, F-34060 Montpellier Université Montpellier 1, F-34000 Montpellier - Université Montpellier 2, F-34000 Montpellier, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Ollendorff
authors.affiliation: Instituto de Física de São Carlos, Universidade de São Paulo, Av. Trabalhador São-Carlense, 400, São Carlos, SP, 13560-970, Brazil.
authors.forename: Igor
authors.initials: I
authors.lastname: Polikarpov
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D008854:Microscopy, Electron; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000378:metabolism; D053838:Scattering, Small Angle; D013329:Structure-Activity Relationship
chemical_list: D004268:DNA-Binding Proteins; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D004247:DNA
keywords: BRET; SAXS; X-ray crystallography; allostery; electron microscopy; nuclear receptor; transcription factor