title: Local motifs involved in the canonical structure of the ligand-binding domain in the nuclear receptor superfamily.
abstract: Structural and sequence alignment analyses have revealed the existence of class-dependent and -independent local motifs involved in the overall fold of the ligand-binding domain (LBD) in the nuclear receptor (NR) superfamily. Of these local motifs, three local motifs, i.e., AF-2 fixed motifs, were involved in the agonist conformation of the activation function-2 (AF-2) region of the LBD. Receptor-agonist interactions increased the stability of these AF-2 fixed motifs in the agonist conformation. In contrast, perturbation of the AF-2 fixed motifs by a ligand or another protein molecule led the AF-2 architecture to adopt an antagonist conformation. Knowledge of this process should provide us with novel insights into the 'agonism' and 'antagonism' of NRs.
authors.affiliation: Institute of Molecular Function, 2-105-14 Takasu, Misato-shi, Saitama 341-0037, Japan. Electronic address: motonori@molfunction.com.
authors.forename: Motonori
authors.initials: M
authors.lastname: Tsuji
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear
keywords: Agonism; Antagonism; Charge–dipole interaction; Local motif; Nuclear receptor ligand-binding domain; Signal amino acid