The smoothened (SMO) receptor, a key signal transducer in the hedgehog signalling pathway, is responsible for the maintenance of normal embryonic development and is implicated in carcinogenesis. It is classified as a class frizzled (class F) G-protein-coupled receptor (GPCR), although the canonical hedgehog signalling pathway involves the GLI transcription factors and the sequence similarity with class A GPCRs is less than 10%. Here we report the crystal structure of the transmembrane domain of the human SMO receptor bound to the small-molecule antagonist LY2940680 at 2.5 Å resolution. Although the SMO receptor shares the seven-transmembrane helical fold, most of the conserved motifs for class A GPCRs are absent, and the structure reveals an unusually complex arrangement of long extracellular loops stabilized by four disulphide bonds. The ligand binds at the extracellular end of the seven-transmembrane- helix bundle and forms extensive contacts with the loops. © 2013 Macmillan Publishers Limited. All rights reserved.
CITATION STYLE
Wang, C., Wu, H., Katritch, V., Han, G. W., Huang, X. P., Liu, W., … Stevens, R. C. (2013). Structure of the human smoothened receptor bound to an antitumour agent. Nature, 497(7449), 338–343. https://doi.org/10.1038/nature12167
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