View source for 9py2


==Engaged-state loperamide-mu opioid receptor-Gi GDPbS complex (rebound)==
<StructureSection load='9py2' size='340' side='right'caption='[[9py2]], [[Resolution|resolution]] 3.16&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9py2]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9PY2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9PY2 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.16&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1CMV:4-[4-(4-chlorophenyl)-4-oxidanyl-piperidin-1-yl]-~{N},~{N}-dimethyl-2,2-diphenyl-butanamide'>A1CMV</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=VSN:5-O-[(R)-hydroxy(thiophosphonooxy)phosphoryl]guanosine'>VSN</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=9py2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9py2 OCA], [https://pdbe.org/9py2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9py2 RCSB], [https://www.ebi.ac.uk/pdbsum/9py2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9py2 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/OPRM_HUMAN OPRM_HUMAN] Receptor for endogenous opioids such as beta-endorphin and endomorphin (PubMed:10529478, PubMed:12589820, PubMed:7891175, PubMed:7905839, PubMed:7957926, PubMed:9689128). Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone (PubMed:10529478, PubMed:10836142, PubMed:12589820, PubMed:19300905, PubMed:7891175, PubMed:7905839, PubMed:7957926, PubMed:9689128). Also activated by enkephalin peptides, such as Met-enkephalin or Met-enkephalin-Arg-Phe, with higher affinity for Met-enkephalin-Arg-Phe (By similarity). 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 (PubMed:7905839). 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 extent to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15 (PubMed:12068084). 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 (By similarity). Also couples to adenylate cyclase stimulatory G alpha proteins (By similarity). The selective temporal coupling to G-proteins and subsequent signaling can be regulated by RGSZ proteins, such as RGS9, RGS17 and RGS4 (By similarity). Phosphorylation by members of the GPRK subfamily of Ser/Thr protein kinases and association with beta-arrestins is involved in short-term receptor desensitization (By similarity). Beta-arrestins associate with the GPRK-phosphorylated receptor and uncouple it from the G-protein thus terminating signal transduction (By similarity). The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits which involves beta-arrestins (By similarity). 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 (By similarity). 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 (By similarity). Receptor down-regulation pathways are varying with the agonist and occur dependent or independent of G-protein coupling (By similarity). Endogenous ligands induce rapid desensitization, endocytosis and recycling (By similarity). Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties (By similarity).[UniProtKB:P33535]<ref>PMID:10529478</ref> <ref>PMID:12068084</ref> <ref>PMID:12589820</ref> <ref>PMID:7891175</ref> <ref>PMID:7905839</ref> <ref>PMID:7957926</ref> <ref>PMID:9689128</ref> <ref>PMID:10836142</ref> <ref>PMID:19300905</ref>   Couples to GNAS and is proposed to be involved in excitatory effects.<ref>PMID:20525224</ref>   Does not bind agonists but may act through oligomerization with binding-competent OPRM1 isoforms and reduce their ligand binding activity.<ref>PMID:16580639</ref>   Does not bind agonists but may act through oligomerization with binding-competent OPRM1 isoforms and reduce their ligand binding activity.<ref>PMID:16580639</ref> [https://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX] Electron-transport protein of unknown function.
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Gati C]]
[[Category: Han GW]]
[[Category: Khan S]]