Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/103764
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dc.contributor.authorRohatgi, Rajaten
dc.contributor.authorNachtergaele, Sigriden
dc.contributor.authorWhalen, Daniel Men
dc.contributor.authorMydock, Laurel Ken
dc.contributor.authorZhao, Zhonghuaen
dc.contributor.authorMalinauskas, Tomasen
dc.contributor.authorKrishnan, Kathiresanen
dc.contributor.authorCovey, Douglas Fen
dc.contributor.authorSiebold, Christianen
dc.contributor.authorIngham, Philip Williamen
dc.date.accessioned2014-05-02T06:05:35Zen
dc.date.accessioned2019-12-06T21:19:40Z-
dc.date.available2014-05-02T06:05:35Zen
dc.date.available2019-12-06T21:19:40Z-
dc.date.copyright2013en
dc.date.issued2013en
dc.identifier.citationNachtergaele, S., Whalen, D. M., Mydock, L. K., Zhao, Z., Malinauskas, T., Krishnan, K., Ingham, P. W., Covey, D. F., Siebold, C., & Rohatgi, R. (2013). Structure and function of the Smoothened extracellular domain in vertebrate Hedgehog signaling. eLife, 2(0), e01340-e01340.en
dc.identifier.issn2050-084Xen
dc.identifier.urihttps://hdl.handle.net/10356/103764-
dc.identifier.urihttp://hdl.handle.net/10220/19293en
dc.description.abstractThe Hedgehog (Hh) signal is transduced across the membrane by the heptahelical protein Smoothened (Smo), a developmental regulator, oncoprotein and drug target in oncology. We present the 2.3 Å crystal structure of the extracellular cysteine rich domain (CRD) of vertebrate Smo and show that it binds to oxysterols, endogenous lipids that activate Hh signaling. The oxysterol-binding groove in the Smo CRD is analogous to that used by Frizzled 8 to bind to the palmitoleyl group of Wnt ligands and to similar pockets used by other Frizzled-like CRDs to bind hydrophobic ligands. The CRD is required for signaling in response to native Hh ligands, showing that it is an important regulatory module for Smo activation. Indeed, targeting of the Smo CRD by oxysterol-inspired small molecules can block signaling by all known classes of Hh activators and by clinically relevant Smo mutants.en
dc.description.sponsorshipASTAR (Agency for Sci., Tech. and Research, S’pore)en
dc.format.extent32 p.en
dc.language.isoenen
dc.relation.ispartofserieseLifeen
dc.rights© 2013 Nachtergaele et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.en
dc.subjectDRNTU::Science::Medicineen
dc.titleStructure and function of the smoothened extracellular domain in vertebrate hedgehog signalingen
dc.typeJournal Articleen
dc.contributor.schoolLee Kong Chian School of Medicine (LKCMedicine)en
dc.identifier.doi10.7554/eLife.01340.001en
dc.description.versionPublished versionen
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item.grantfulltextopen-
Appears in Collections:LKCMedicine Journal Articles

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