View source for 5v56


==2.9A XFEL structure of the multi-domain human smoothened receptor (with E194M mutation) in complex with TC114==
<StructureSection load='5v56' size='340' side='right'caption='[[5v56]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5v56]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Desulfovibrio_vulgaris_str._Hildenborough Desulfovibrio vulgaris str. Hildenborough] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V56 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5V56 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]] 2.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=836:N-METHYL-N-[1-[4-(2-METHYLPYRAZOL-3-YL)PHTHALAZIN-1-YL]PIPERIDIN-4-YL]-4-NITRO-2-(TRIFLUOROMETHYL)BENZAMIDE'>836</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=5v56 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v56 OCA], [https://pdbe.org/5v56 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5v56 RCSB], [https://www.ebi.ac.uk/pdbsum/5v56 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5v56 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SMO_HUMAN SMO_HUMAN] G protein-coupled receptor that probably associates with the patched protein (PTCH) to transduce the hedgehog's proteins signal. Binding of sonic hedgehog (SHH) to its receptor patched is thought to prevent normal inhibition by patched of smoothened (SMO). Required for the accumulation of KIF7 and GLI3 in the cilia.<ref>PMID:19592253</ref> [https://www.uniprot.org/uniprot/FLAV_DESVH FLAV_DESVH] Low-potential electron donor to a number of redox enzymes.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The Smoothened receptor (SMO) belongs to the Class Frizzled of the G protein-coupled receptor (GPCR) superfamily, constituting a key component of the Hedgehog signalling pathway. Here we report the crystal structure of the multi-domain human SMO, bound and stabilized by a designed tool ligand TC114, using an X-ray free-electron laser source at 2.9 A. The structure reveals a precise arrangement of three distinct domains: a seven-transmembrane helices domain (TMD), a hinge domain (HD) and an intact extracellular cysteine-rich domain (CRD). This architecture enables allosteric interactions between the domains that are important for ligand recognition and receptor activation. By combining the structural data, molecular dynamics simulation, and hydrogen-deuterium-exchange analysis, we demonstrate that transmembrane helix VI, extracellular loop 3 and the HD play a central role in transmitting the signal employing a unique GPCR activation mechanism, distinct from other multi-domain GPCRs.

Crystal structure of a multi-domain human smoothened receptor in complex with a super stabilizing ligand.,Zhang X, Zhao F, Wu Y, Yang J, Han GW, Zhao S, Ishchenko A, Ye L, Lin X, Ding K, Dharmarajan V, Griffin PR, Gati C, Nelson G, Hunter MS, Hanson MA, Cherezov V, Stevens RC, Tan W, Tao H, Xu F Nat Commun. 2017 May 17;8:15383. doi: 10.1038/ncomms15383. PMID:28513578<ref>PMID:28513578</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5v56" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Desulfovibrio vulgaris str. Hildenborough]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cherezov V]]
[[Category: Dharmarajan V]]
[[Category: Ding K]]
[[Category: Gati C]]
[[Category: Griffin PR]]
[[Category: Han GW]]
[[Category: Hanson MA]]
[[Category: Hunter MS]]
[[Category: Ishchenko A]]
[[Category: Lin X]]
[[Category: Nelson G]]
[[Category: Stevens RC]]
[[Category: Tan W]]
[[Category: Tao H]]
[[Category: Wu Y]]
[[Category: Xu F]]
[[Category: Yang J]]
[[Category: Ye L]]
[[Category: Zhang X]]
[[Category: Zhao F]]
[[Category: Zhao S]]