5kzv

Crystal structure of the xenopus Smoothened cysteine-rich domain (CRD) in complex with 20(S)-hydroxycholesterol

spinqualitylabelsall models 5kzv, resolution 1.62Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5kzv is a 1 chain structure with sequence from Xenopus laevis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.616Å Ligands: HCD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q98SW5_XENLA Publication Abstract from PubMed In vertebrates, sterols are necessary for Hedgehog signaling, a pathway critical in embryogenesis and cancer. Sterols activate the membrane protein Smoothened by binding its extracellular, cysteine-rich domain (CRD). Major unanswered questions concern the nature of the endogenous, activating sterol and the mechanism by which it regulates Smoothened. We report crystal structures of CRD complexed with sterols and alone, revealing that sterols induce a dramatic conformational change of the binding site, which is sufficient for Smoothened activation and is unique among CRD-containing receptors. We demonstrate that Hedgehog signaling requires sterol binding to Smoothened and define key residues for sterol recognition and activity. We also show that cholesterol itself binds and activates Smoothened. Furthermore, the effect of oxysterols is abolished in Smoothened mutants that retain activation by cholesterol and Hedgehog. We propose that the endogenous Smoothened activator is cholesterol, not oxysterols, and that vertebrate Hedgehog signaling controls Smoothened by regulating its access to cholesterol. Cellular Cholesterol Directly Activates Smoothened in Hedgehog Signaling.,Huang P, Nedelcu D, Watanabe M, Jao C, Kim Y, Liu J, Salic A Cell. 2016 Aug 25;166(5):1176-1187.e14. doi: 10.1016/j.cell.2016.08.003. Epub, 2016 Aug 18. PMID:27545348 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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