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Structural insights into the role of the Smoothened cysteine-rich domain in Hedgehog signalling

Author

Listed:
  • Rajashree Rana

    (St Jude Children’s Research Hospital
    Integrated Program in Biomedical Sciences, University of Tennessee Health Science Center)

  • Candace E. Carroll

    (St Jude Children’s Research Hospital
    Present address: Hardin Simmons University, Abilene, Texas, USA)

  • Ho-Jin Lee

    (St Jude Children’s Research Hospital)

  • Ju Bao

    (St Jude Children’s Research Hospital)

  • Suresh Marada

    (St Jude Children’s Research Hospital)

  • Christy R.R. Grace

    (St Jude Children’s Research Hospital)

  • Cristina D. Guibao

    (St Jude Children’s Research Hospital)

  • Stacey K. Ogden

    (Integrated Program in Biomedical Sciences, University of Tennessee Health Science Center
    St Jude Children’s Research Hospital)

  • Jie J. Zheng

    (St Jude Children’s Research Hospital
    Integrated Program in Biomedical Sciences, University of Tennessee Health Science Center)

Abstract

Smoothened (Smo) is a member of the Frizzled (FzD) class of G-protein-coupled receptors (GPCRs), and functions as the key transducer in the Hedgehog (Hh) signalling pathway. Smo has an extracellular cysteine-rich domain (CRD), indispensable for its function and downstream Hh signalling. Despite its essential role, the functional contribution of the CRD to Smo signalling has not been clearly elucidated. However, given that the FzD CRD binds to the endogenous Wnt ligand, it has been proposed that the Smo CRD may bind its own endogenous ligand. Here we present the NMR solution structure of the Drosophila Smo CRD, and describe interactions between the glucocorticoid budesonide (Bud) and the Smo CRDs from both Drosophila and human. Our results highlight a function of the Smo CRD, demonstrating its role in binding to small-molecule modulators.

Suggested Citation

  • Rajashree Rana & Candace E. Carroll & Ho-Jin Lee & Ju Bao & Suresh Marada & Christy R.R. Grace & Cristina D. Guibao & Stacey K. Ogden & Jie J. Zheng, 2013. "Structural insights into the role of the Smoothened cysteine-rich domain in Hedgehog signalling," Nature Communications, Nature, vol. 4(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3965
    DOI: 10.1038/ncomms3965
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