|
|
| Line 1: |
Line 1: |
| | | | |
| | ==1.8 A Structure of the human delta opioid 7TM receptor (PSI Community Target)== | | ==1.8 A Structure of the human delta opioid 7TM receptor (PSI Community Target)== |
| - | <StructureSection load='4n6h' size='340' side='right' caption='[[4n6h]], [[Resolution|resolution]] 1.80Å' scene=''> | + | <StructureSection load='4n6h' size='340' side='right'caption='[[4n6h]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4n6h]] 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=4N6H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4N6H FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4n6h]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] 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=4N6H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4N6H FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EJ4:(4BS,8R,8AS,14BR)-7-(CYCLOPROPYLMETHYL)-5,6,7,8,14,14B-HEXAHYDRO-4,8-METHANO[1]BENZOFURO[2,3-A]PYRIDO[4,3-B]CARBAZOLE-1,8A(9H)-DIOL'>EJ4</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EJ4:(4BS,8R,8AS,14BR)-7-(CYCLOPROPYLMETHYL)-5,6,7,8,14,14B-HEXAHYDRO-4,8-METHANO[1]BENZOFURO[2,3-A]PYRIDO[4,3-B]CARBAZOLE-1,8A(9H)-DIOL'>EJ4</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ej4|4ej4]]</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=4n6h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n6h OCA], [https://pdbe.org/4n6h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4n6h RCSB], [https://www.ebi.ac.uk/pdbsum/4n6h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4n6h ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">OPRD, OPRD1 ([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=4n6h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n6h OCA], [http://pdbe.org/4n6h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4n6h RCSB], [http://www.ebi.ac.uk/pdbsum/4n6h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4n6h ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX]] Electron-transport protein of unknown function. | + | [https://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX] Electron-transport protein of unknown function.[https://www.uniprot.org/uniprot/OPRD_HUMAN OPRD_HUMAN] G-protein coupled receptor that functions as receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain and in opiate-mediated analgesia. Plays a role in developing analgesic tolerance to morphine.<ref>PMID:22184124</ref> <ref>PMID:7808419</ref> <ref>PMID:8201839</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 24: |
Line 22: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacillus coli migula 1895]] | + | [[Category: Escherichia coli]] |
| - | [[Category: Cherezov, V]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Fenalti, G]] | + | [[Category: Large Structures]] |
| - | [[Category: GPCR, GPCR Network]] | + | [[Category: Cherezov V]] |
| - | [[Category: Giguere, P M]] | + | [[Category: Fenalti G]] |
| - | [[Category: Han, G W]] | + | [[Category: Giguere PM]] |
| - | [[Category: Huang, X P]] | + | [[Category: Han GW]] |
| - | [[Category: Katritch, V]] | + | [[Category: Huang X-P]] |
| - | [[Category: Roth, B L]] | + | [[Category: Katritch V]] |
| - | [[Category: Stevens, R C]] | + | [[Category: Roth BL]] |
| - | [[Category: Thompson, A A]] | + | [[Category: Stevens RC]] |
| - | [[Category: Allostery]]
| + | [[Category: Thompson AA]] |
| - | [[Category: Constitutive activity]]
| + | |
| - | [[Category: Functional selectivity]]
| + | |
| - | [[Category: Gpcr]]
| + | |
| - | [[Category: Gpcr network]]
| + | |
| - | [[Category: Gpcr signaling]]
| + | |
| - | [[Category: Human opioid receptor]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Psi-biology]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| - | [[Category: Sodium regulation]]
| + | |
| - | [[Category: Structural genomic]]
| + | |
| Structural highlights
4n6h is a 1 chain structure with sequence from Escherichia coli and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
C562_ECOLX Electron-transport protein of unknown function.OPRD_HUMAN G-protein coupled receptor that functions as receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain and in opiate-mediated analgesia. Plays a role in developing analgesic tolerance to morphine.[1] [2] [3]
Publication Abstract from PubMed
Opioids represent widely prescribed and abused medications, although their signal transduction mechanisms are not well understood. Here we present the 1.8 A high-resolution crystal structure of the human delta-opioid receptor (delta-OR), revealing the presence and fundamental role of a sodium ion in mediating allosteric control of receptor functional selectivity and constitutive activity. The distinctive delta-OR sodium ion site architecture is centrally located in a polar interaction network in the seven-transmembrane bundle core, with the sodium ion stabilizing a reduced agonist affinity state, and thereby modulating signal transduction. Site-directed mutagenesis and functional studies reveal that changing the allosteric sodium site residue Asn 131 to an alanine or a valine augments constitutive beta-arrestin-mediated signalling. Asp95Ala, Asn310Ala and Asn314Ala mutations transform classical delta-opioid antagonists such as naltrindole into potent beta-arrestin-biased agonists. The data establish the molecular basis for allosteric sodium ion control in opioid signalling, revealing that sodium-coordinating residues act as 'efficacy switches' at a prototypic G-protein-coupled receptor.
Molecular control of delta-opioid receptor signalling.,Fenalti G, Giguere PM, Katritch V, Huang XP, Thompson AA, Cherezov V, Roth BL, Stevens RC Nature. 2014 Feb 13;506(7487):191-6. doi: 10.1038/nature12944. Epub 2014 Jan 12. PMID:24413399[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Leskela TT, Lackman JJ, Vierimaa MM, Kobayashi H, Bouvier M, Petaja-Repo UE. Cys-27 variant of human delta-opioid receptor modulates maturation and cell surface delivery of Phe-27 variant via heteromerization. J Biol Chem. 2012 Feb 10;287(7):5008-20. doi: 10.1074/jbc.M111.305656. Epub 2011 , Dec 19. PMID:22184124 doi:http://dx.doi.org/10.1074/jbc.M111.305656
- ↑ Simonin F, Befort K, Gaveriaux-Ruff C, Matthes H, Nappey V, Lannes B, Micheletti G, Kieffer B. The human delta-opioid receptor: genomic organization, cDNA cloning, functional expression, and distribution in human brain. Mol Pharmacol. 1994 Dec;46(6):1015-21. PMID:7808419
- ↑ Knapp RJ, Malatynska E, Fang L, Li X, Babin E, Nguyen M, Santoro G, Varga EV, Hruby VJ, Roeske WR, et al.. Identification of a human delta opioid receptor: cloning and expression. Life Sci. 1994;54(25):PL463-9. PMID:8201839
- ↑ Fenalti G, Giguere PM, Katritch V, Huang XP, Thompson AA, Cherezov V, Roth BL, Stevens RC. Molecular control of delta-opioid receptor signalling. Nature. 2014 Feb 13;506(7487):191-6. doi: 10.1038/nature12944. Epub 2014 Jan 12. PMID:24413399 doi:http://dx.doi.org/10.1038/nature12944
|
