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5v56

From Proteopedia

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Current revision

2.9A XFEL structure of the multi-domain human smoothened receptor (with E194M mutation) in complex with TC114

Structural highlights

5v56 is a 2 chain structure with sequence from Desulfovibrio vulgaris str. Hildenborough and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.9Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] FLAV_DESVH Low-potential electron donor to a number of redox enzymes.

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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Endoh-Yamagami S, Evangelista M, Wilson D, Wen X, Theunissen JW, Phamluong K, Davis M, Scales SJ, Solloway MJ, de Sauvage FJ, Peterson AS. The mammalian Cos2 homolog Kif7 plays an essential role in modulating Hh signal transduction during development. Curr Biol. 2009 Aug 11;19(15):1320-6. doi: 10.1016/j.cub.2009.06.046. Epub 2009, Jul 9. PMID:19592253 doi:http://dx.doi.org/10.1016/j.cub.2009.06.046
↑ 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. Crystal structure of a multi-domain human smoothened receptor in complex with a super stabilizing ligand. Nat Commun. 2017 May 17;8:15383. doi: 10.1038/ncomms15383. PMID:28513578 doi:http://dx.doi.org/10.1038/ncomms15383

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5v56"

@@ Line 1: / Line 1: @@
 ==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=''>
+<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. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5V56 FirstGlance]. <br>
+<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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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>
+</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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5v57|5v57]]</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5v56 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v56 OCA], [http://pdbe.org/5v56 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5v56 RCSB], [http://www.ebi.ac.uk/pdbsum/5v56 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5v56 ProSAT]</span></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 ==
-[[http://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/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 ==
@@ Line 23: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Cherezov, V]]
+[[Category: Desulfovibrio vulgaris str. Hildenborough]]
-[[Category: Dharmarajan, V]]
+[[Category: Homo sapiens]]
-[[Category: Ding, K]]
+[[Category: Large Structures]]
-[[Category: Gati, C]]
+[[Category: Cherezov V]]
-[[Category: Griffin, P R]]
+[[Category: Dharmarajan V]]
-[[Category: Han, G W]]
+[[Category: Ding K]]
-[[Category: Hanson, M A]]
+[[Category: Gati C]]
-[[Category: Hunter, M S]]
+[[Category: Griffin PR]]
-[[Category: Ishchenko, A]]
+[[Category: Han GW]]
-[[Category: Lin, X]]
+[[Category: Hanson MA]]
-[[Category: Nelson, G]]
+[[Category: Hunter MS]]
-[[Category: Stevens, R C]]
+[[Category: Ishchenko A]]
-[[Category: Tan, W]]
+[[Category: Lin X]]
-[[Category: Tao, H]]
+[[Category: Nelson G]]
-[[Category: Wu, Y]]
+[[Category: Stevens RC]]
-[[Category: Xu, F]]
+[[Category: Tan W]]
-[[Category: Yang, J]]
+[[Category: Tao H]]
-[[Category: Ye, L]]
+[[Category: Wu Y]]
-[[Category: Zhang, X]]
+[[Category: Xu F]]
-[[Category: Zhao, F]]
+[[Category: Yang J]]
-[[Category: Zhao, S]]
+[[Category: Ye L]]
-[[Category: 7tm domain]]
+[[Category: Zhang X]]
-[[Category: Class f]]
+[[Category: Zhao F]]
-[[Category: Extracellular cystein-rich domain]]
+[[Category: Zhao S]]
-[[Category: Flavodoxin]]
-[[Category: Gpcr]]
-[[Category: Gpcr hedgehog signaling]]
-[[Category: Hinge domain]]
-[[Category: Human smoothened receptor complex]]
-[[Category: Lcp]]
-[[Category: Membrane protein]]
-[[Category: Tc114]]
-[[Category: Xfel]]

5v56

From Proteopedia

Current revision

2.9A XFEL structure of the multi-domain human smoothened receptor (with E194M mutation) in complex with TC114

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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