title: [Structure of the Smoothened receptor].
abstract: The Smoothened (Smo) receptor is a major component involved in signal transduction of the Hedgehog (Hh) morphogens both during embryogenesis and in the adult. Smo antagonists represent a promi-sing alternative for the treatment of cancers linked to abnormal Hh signalling. The crystal structure of the human Smo receptor bound to an antitumour agent demonstrates that this receptor belongs to the superfamily of G-protein coupled receptors. The antagonist binds to a pocket localized at the extracellular side formed by the seven transmembrane domains and the complex arrangement of the unusually long extracellular loops. The structure of the Smo receptor will promote the development of small molecules interacting with a key therapeutic target with interests in regenerative medicine and cancer.
authors.affiliation: CNRS, Institut de neurobiologie Alfred Fessard, laboratoire de neurobiologie et du développement, UPR 3294, équipe transduction du signal et neuropharmacologie développementale, bâtiment 33, 1, avenue de la Terrasse, 91198 Gif-sur-Yvette, France.
authors.forename: Martial
authors.initials: M
authors.lastname: Ruat
authors.forename: Lucile
authors.initials: L
authors.lastname: Hoch
authors.forename: Hélène
authors.initials: H
authors.lastname: Faure
authors.forename: Didier
authors.initials: D
authors.lastname: Rognan
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003461:Crystallography; D006801:Humans; D008958:Models, Molecular; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000235:genetics / Q000628:therapy; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000235:genetics; D000072086:Smoothened Receptor
chemical_list: D000970:Antineoplastic Agents; D043562:Receptors, G-Protein-Coupled; C491023:SMO protein, human; D000072086:Smoothened Receptor