6d35: Difference between revisions
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<StructureSection load='6d35' size='340' side='right' caption='[[6d35]], [[Resolution|resolution]] 3.90Å' scene=''> | <StructureSection load='6d35' size='340' side='right' caption='[[6d35]], [[Resolution|resolution]] 3.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6d35]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D35 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D35 FirstGlance]. <br> | <table><tr><td colspan='2'>[[6d35]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D35 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D35 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">smo, Smo ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</td></tr> | |||
<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=6d35 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d35 OCA], [http://pdbe.org/6d35 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d35 RCSB], [http://www.ebi.ac.uk/pdbsum/6d35 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d35 ProSAT]</span></td></tr> | <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=6d35 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d35 OCA], [http://pdbe.org/6d35 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d35 RCSB], [http://www.ebi.ac.uk/pdbsum/6d35 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d35 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The seven-transmembrane-spanning protein Smoothened is the central transducer in Hedgehog signaling, a pathway fundamental in development and in cancer. Smoothened is activated by cholesterol binding to its extracellular cysteine-rich domain (CRD). How this interaction leads to changes in the transmembrane domain and Smoothened activation is unknown. Here, we report crystal structures of sterol-activated Smoothened. The CRD undergoes a dramatic reorientation, allosterically causing the transmembrane domain to adopt a conformation similar to active G-protein-coupled receptors. We show that Smoothened contains a unique inhibitory pi-cation lock, which is broken on activation and is disrupted in constitutively active oncogenic mutants. Smoothened activation opens a hydrophobic tunnel, suggesting a pathway for cholesterol movement from the inner membrane leaflet to the CRD. All Smoothened antagonists bind the transmembrane domain and block tunnel opening, but cyclopamine also binds the CRD, inducing the active transmembrane conformation. Together, these results define the mechanisms of Smoothened activation and inhibition. | |||
Structural Basis of Smoothened Activation in Hedgehog Signaling.,Huang P, Zheng S, Wierbowski BM, Kim Y, Nedelcu D, Aravena L, Liu J, Kruse AC, Salic A Cell. 2018 May 15. pii: S0092-8674(18)30522-1. doi: 10.1016/j.cell.2018.04.029. PMID:29804838<ref>PMID:29804838</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6d35" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Bacillus coli migula 1895]] | |||
[[Category: Huang, P]] | [[Category: Huang, P]] | ||
[[Category: Kim, Y]] | [[Category: Kim, Y]] | ||
Revision as of 11:10, 14 June 2018
Crystal structure of Xenopus Smoothened in complex with cholesterolCrystal structure of Xenopus Smoothened in complex with cholesterol
Structural highlights
Publication Abstract from PubMedThe seven-transmembrane-spanning protein Smoothened is the central transducer in Hedgehog signaling, a pathway fundamental in development and in cancer. Smoothened is activated by cholesterol binding to its extracellular cysteine-rich domain (CRD). How this interaction leads to changes in the transmembrane domain and Smoothened activation is unknown. Here, we report crystal structures of sterol-activated Smoothened. The CRD undergoes a dramatic reorientation, allosterically causing the transmembrane domain to adopt a conformation similar to active G-protein-coupled receptors. We show that Smoothened contains a unique inhibitory pi-cation lock, which is broken on activation and is disrupted in constitutively active oncogenic mutants. Smoothened activation opens a hydrophobic tunnel, suggesting a pathway for cholesterol movement from the inner membrane leaflet to the CRD. All Smoothened antagonists bind the transmembrane domain and block tunnel opening, but cyclopamine also binds the CRD, inducing the active transmembrane conformation. Together, these results define the mechanisms of Smoothened activation and inhibition. Structural Basis of Smoothened Activation in Hedgehog Signaling.,Huang P, Zheng S, Wierbowski BM, Kim Y, Nedelcu D, Aravena L, Liu J, Kruse AC, Salic A Cell. 2018 May 15. pii: S0092-8674(18)30522-1. doi: 10.1016/j.cell.2018.04.029. PMID:29804838[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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