2mah
From Proteopedia
Solution structure of Smoothened
Structural highlights
FunctionSMO_DROME Segment polarity protein required for correct patterning of every segment. G protein-coupled receptor that associates with the patched protein (ptc) to transduce the hedgehog (hh) signal through the activation of an inhibitory G-protein. In the absence of hh, ptc represses the constitutive signaling activity of smo through fused (fu). Publication Abstract from PubMedSmoothened (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. Structural insights into the role of the Smoothened cysteine-rich domain in Hedgehog signalling.,Rana R, Carroll CE, Lee HJ, Bao J, Marada S, Grace CR, Guibao CD, Ogden SK, Zheng JJ Nat Commun. 2013;4:2965. doi: 10.1038/ncomms3965. PMID:24351982[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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