[Structure of the Smoothened receptor].

Med Sci (Paris)

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.

Published: October 2013

AI Article Synopsis

  • The Smoothened (Smo) receptor plays a crucial role in transmitting signals from Hedgehog morphogens during both development and adulthood.
  • Smo antagonists show potential as cancer treatments by targeting abnormal Hedgehog signaling pathways.
  • The crystal structure of the Smo receptor bound to an antitumor agent reveals its classification as a G-protein coupled receptor and highlights the structure's importance for developing new therapeutic molecules.

Article 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.

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Source
http://dx.doi.org/10.1051/medsci/20132910012DOI Listing

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