5c1m: Difference between revisions
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''' | ==Crystal structure of active mu-opioid receptor bound to the agonist BU72== | ||
<StructureSection load='5c1m' size='340' side='right' caption='[[5c1m]], [[Resolution|resolution]] 2.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5c1m]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5C1M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5C1M FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4VO:(2S,3S,3AR,5AR,6R,11BR,11CS)-3A-METHOXY-3,14-DIMETHYL-2-PHENYL-2,3,3A,6,7,11C-HEXAHYDRO-1H-6,11B-(EPIMINOETHANO)-3,5A-METHANONAPHTHO[2,1-G]INDOL-10-OL'>4VO</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=P6G:HEXAETHYLENE+GLYCOL'>P6G</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | |||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=YCM:S-(2-AMINO-2-OXOETHYL)-L-CYSTEINE'>YCM</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4dkl|4dkl]]</td></tr> | |||
[[Category: | <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=5c1m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5c1m OCA], [http://www.rcsb.org/pdb/explore.do?structureId=5c1m RCSB], [http://www.ebi.ac.uk/pdbsum/5c1m PDBsum]</span></td></tr> | ||
[[Category: | </table> | ||
[[Category: Husbands, S | == Function == | ||
[[http://www.uniprot.org/uniprot/OPRM_MOUSE OPRM_MOUSE]] Receptor for endogenous opioids such as beta-endorphin and endomorphin. Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociation of the G-protein complex with the free GTP-bound G-protein alpha and the G-protein beta-gamma dimer activating downstream cellular effectors. The agonist- and cell type-specific activity is predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1 and Alpha-2, and to a lesser extend to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15. They mediate an array of downstream cellular responses, including inhibition of adenylate cyclase activity and both N-type and L-type calcium channels, activation of inward rectifying potassium channels, mitogen-activated protein kinase (MAPK), phospholipase C (PLC), phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K) and regulation of NF-kappa-B. Also couples to adenylate cyclase stimulatory G alpha proteins. The selective temporal coupling to G-proteins and subsequent signaling can be regulated by RGSZ proteins, such as RGS9, RGS17 and RGS4. Phosphorylation by members of the GPRK subfamily of Ser/Thr protein kinases and association with beta-arrestins is involved in short-term receptor desensitization. Beta-arrestins associate with the GPRK-phosphorylated receptor and uncouple it from the G-protein thus terminating signal transduction. The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits which involves beta-arrestins. The activation of the ERK pathway occurs either in a G-protein-dependent or a beta-arrestin-dependent manner and is regulated by agonist-specific receptor phosphorylation. Acts as a class A G-protein coupled receptor (GPCR) which dissociates from beta-arrestin at or near the plasma membrane and undergoes rapid recycling. Receptor down-regulation pathways are varying with the agonist and occur dependent or independent of G-protein coupling. Endogenous ligands induce rapid desensitization, endocytosis and recycling. Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties. Involved in neurogenesis. Isoform 9 is involved in morphine-induced scratching and seems to cross-activate GRPR in response to morphine.<ref>PMID:10842167</ref> <ref>PMID:16682964</ref> <ref>PMID:21422164</ref> <ref>PMID:22437502</ref> <ref>PMID:7797593</ref> <ref>PMID:9037090</ref> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Dror, R O]] | |||
[[Category: Feinberg, E N]] | |||
[[Category: Gmeiner, P]] | |||
[[Category: Granier, S]] | |||
[[Category: Huang, W J]] | |||
[[Category: Husbands, S M]] | |||
[[Category: Kato, H E]] | |||
[[Category: Kling, R]] | [[Category: Kling, R]] | ||
[[Category: | [[Category: Kobilka, B K]] | ||
[[Category: | [[Category: Laeremans, T]] | ||
[[Category: | [[Category: Livingston, K E]] | ||
[[Category: | [[Category: Manglik, A]] | ||
[[Category: Sanborn, A | [[Category: Sanborn, A L]] | ||
[[Category: Steyaert, J]] | [[Category: Steyaert, J]] | ||
[[Category: | [[Category: Thorsen, T S]] | ||
[[Category: | [[Category: Traynor, J R]] | ||
[[Category: | [[Category: Venkatakrishnan, A J]] | ||
[[Category: | [[Category: Weis, W I]] | ||
[[Category: | [[Category: Activation]] | ||
[[Category: | [[Category: Agonist]] | ||
[[Category: | [[Category: Ligand]] | ||
[[Category: | [[Category: Mice]] | ||
[[Category: | [[Category: Morphinan]] | ||
[[Category: Mu]] | |||
[[Category: Nanobody]] | |||
[[Category: Opioid]] | |||
[[Category: Receptor]] | |||
[[Category: Signaling protein-antagonist complex]] | |||