title: Activation of nuclear receptors: a perspective from structural genomics.
abstract: Crystal structures of more than two dozen different nuclear receptor ligand binding domains have defined a simple paradigm of receptor activation, in which agonist binding induces the activation function-2 (AF-2) helix to form a charge clamp for coactivator recruitment. Recent structural studies present a surprising contrast. Activation of the mouse LRH-1 receptor is independent of a bound agonist despite its large ligand binding pocket, whereas the activation of the Drosophila DHR38 receptor is dependent on ecdysteroids even though the receptor lacks a ligand binding pocket. These new findings shed light on the diverse structural mechanisms that nuclear receptors have evolved for activation, and have important implications in their respective signaling pathways.
authors.affiliation: Laboratory of Structural Sciences, Van Andel Research Institute, 333 Bostwick Avenue, Grand Rapids, MI 49503, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Millard H
authors.initials: MH
authors.lastname: Lambert
authors.forename: H Eric
authors.initials: HE
authors.lastname: Xu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004330:Drosophila; D023281:Genomics; D008969:Molecular Sequence Data; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D017386:Sequence Homology, Amino Acid
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear