title: Structural analysis of nuclear receptors: from isolated domains to integral proteins.
abstract: Nuclear receptors (NRs) are ligand dependent transcription factors that regulate gene expression. A number of in depth structure-function relationship studies have been performed, in particular with drug design perspectives. Recent structural results concerning integral receptors in diverse functional states, obtained using a combination of different methods, now allow a better understanding of the mechanisms involved in molecular regulation. The structural data highlight the importance of DNA sequences for binding selectivity and the role of promoter response elements in the spatial organization of the protein domains into functional complexes. The solution structures of several heterodimer complexes reveal how the DNA directs the positioning of coactivators. In the case of PPARγ-RXRα the comparison with the crystal structure reveals two different conformational states that illustrate the flexibility of the receptors. The results shed light on the dynamics of the molecular recognition process.
authors: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut National de la Santé et de la Recherche Médicale U964/Centre National de Recherche Scientifique UMR7104/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch, France.
authors: Yann
authors: Y
authors: Brélivet
authors: Natacha
authors: N
authors: Rochel
authors: Dino
authors: D
authors: Moras
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D056970:Co-Repressor Proteins / Q000737:chemistry; D004247:DNA / Q000737:chemistry; D005786:Gene Expression Regulation; D006801:Humans; D046911:Macromolecular Substances / Q000737:chemistry; D008958:Models, Molecular; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry*
chemical_list: D056970:Co-Repressor Proteins; D046911:Macromolecular Substances; D018160:Receptors, Cytoplasmic and Nuclear; D004247:DNA