View source for 5kzz


==Crystal structure of the xenopus Smoothened cysteine-rich domain (CRD) in its apo-form==
<StructureSection load='5kzz' size='340' side='right'caption='[[5kzz]], [[Resolution|resolution]] 1.33&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5kzz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KZZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KZZ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.332&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5kzz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kzz OCA], [https://pdbe.org/5kzz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kzz RCSB], [https://www.ebi.ac.uk/pdbsum/5kzz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kzz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q98SW5_XENLA Q98SW5_XENLA] 
<div style="background-color:#fffaf0;">
== 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<ref>PMID:27545348</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5kzz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Xenopus laevis]]
[[Category: Huang P]]
[[Category: Kim Y]]
[[Category: Salic A]]