title: Signature of the oligomeric behaviour of nuclear receptors at the sequence and structural level.
abstract: Nuclear receptors (NRs) are ligand-dependent transcription factors that control a large number of physiological events through the regulation of gene transcription. NRs function either as homodimers or as heterodimers with retinoid X receptor/ultraspiracle protein (RXR/USP). A structure-based sequence analysis aimed at discovering the molecular mechanism that controls the dimeric association of the ligand-binding domain reveals two sets of differentially conserved residues, which partition the entire NR superfamily into two classes related to their oligomeric behaviour. Site-directed mutagenesis confirms the functional importance of these residues for the dimerization process and/or transcriptional activity. All homodimers belong to class I, in which the related residues contribute a communication pathway of two salt bridges linking helix 1 on the cofactor-binding site to the dimer interface. A salt bridge involving a differentially conserved arginine residue in loop H8-H9 defines the signature motif of heterodimers. RXR/USP and all Caenorhabditis elegans NRs belong to class I, supporting the hypothesis of an earlier emergence of this class.
authors.affiliation: Département de Biologie et Génomique Structurales, IGBMC, 1 rue Laurent Fries, 67404 Illkirch, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Brelivet
authors.forename: Sabrina
authors.initials: S
authors.lastname: Kammerer
authors.forename: Natacha
authors.initials: N
authors.lastname: Rochel
authors.forename: Olivier
authors.initials: O
authors.lastname: Poch
authors.forename: Dino
authors.initials: D
authors.lastname: Moras
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019281:Dimerization; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear