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4c7a

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==Crystal structure of the Smoothened CRD, selenomethionine-labeled==
==Crystal structure of the Smoothened CRD, selenomethionine-labeled==
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<StructureSection load='4c7a' size='340' side='right' caption='[[4c7a]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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<StructureSection load='4c7a' size='340' side='right'caption='[[4c7a]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4c7a]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Brachidanio_rerio Brachidanio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C7A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4C7A FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4c7a]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C7A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4C7A FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4c7a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c7a OCA], [https://pdbe.org/4c7a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4c7a RCSB], [https://www.ebi.ac.uk/pdbsum/4c7a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4c7a ProSAT]</span></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4c79|4c79]]</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4c7a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c7a OCA], [http://pdbe.org/4c7a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4c7a RCSB], [http://www.ebi.ac.uk/pdbsum/4c7a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4c7a ProSAT]</span></td></tr>
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</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[[https://www.uniprot.org/uniprot/Q90X26_DANRE Q90X26_DANRE]]
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The 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 A 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. DOI:http://dx.doi.org/10.7554/eLife.01340.001.
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Structure and function of the Smoothened extracellular domain in vertebrate Hedgehog signaling.,Nachtergaele S, Whalen DM, Mydock LK, Zhao Z, Malinauskas T, Krishnan K, Ingham PW, Covey DF, Siebold C, Rohatgi R Elife. 2013 Oct 29;2:e01340. doi: 10.7554/eLife.01340. PMID:24171105<ref>PMID:24171105</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4c7a" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Brachidanio rerio]]
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[[Category: Danio rerio]]
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[[Category: Covey, D F]]
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[[Category: Large Structures]]
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[[Category: Ingham, P W]]
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[[Category: Covey DF]]
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[[Category: Krishnan, K]]
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[[Category: Ingham PW]]
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[[Category: Malinauskas, T]]
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[[Category: Krishnan K]]
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[[Category: Mydock, L K]]
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[[Category: Malinauskas T]]
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[[Category: Nachtergaele, S]]
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[[Category: Mydock LK]]
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[[Category: Rohatgi, R]]
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[[Category: Nachtergaele S]]
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[[Category: Siebold, C]]
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[[Category: Rohatgi R]]
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[[Category: Whalen, D M]]
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[[Category: Siebold C]]
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[[Category: Zhao, Z]]
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[[Category: Whalen DM]]
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[[Category: Signaling protein]]
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[[Category: Zhao Z]]

Current revision

Crystal structure of the Smoothened CRD, selenomethionine-labeled

PDB ID 4c7a

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