5v56: Difference between revisions

Revision as of 16:53, 20 November 2019

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 Desvh. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	836, FMN, NAG
Related:	5v57
Gene:	SMO, SMOH (DESVH)
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]

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:https://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:https://dx.doi.org/10.1038/ncomms15383

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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:https://dx.doi.org/10.1016/j.cub.2009.06.046

[2] 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:https://dx.doi.org/10.1038/ncomms15383

[1]

[2]

@@ 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 [http://en.wikipedia.org/wiki/Desvh Desvh]. 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>
 </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>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5v57|5v57]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SMO, SMOH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=882 DESVH])</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>
 </table>
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Desvh]]
+[[Category: Large Structures]]
 [[Category: Cherezov, V]]
 [[Category: Dharmarajan, V]]

5v56: Difference between revisions

Revision as of 16:53, 20 November 2019

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

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