View source for 8efq


==DAMGO-bound mu-opioid receptor-Gi complex==
<StructureSection load='8efq' size='340' side='right'caption='[[8efq]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8efq]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8EFQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8EFQ 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]] 3.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=ETA:ETHANOLAMINE'>ETA</scene>, <scene name='pdbligand=MEA:N-METHYLPHENYLALANINE'>MEA</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=8efq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8efq OCA], [https://pdbe.org/8efq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8efq RCSB], [https://www.ebi.ac.uk/pdbsum/8efq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8efq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GNAI1_HUMAN GNAI1_HUMAN] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division.<ref>PMID:17635935</ref> <ref>PMID:17264214</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Morphine and fentanyl are among the most used opioid drugs that confer analgesia and unwanted side effects through both G protein and arrestin signaling pathways of mu-opioid receptor (muOR). Here, we report structures of the human muOR-G protein complexes bound to morphine and fentanyl, which uncover key differences in how they bind the receptor. We also report structures of muOR bound to TRV130, PZM21, and SR17018, which reveal preferential interactions of these agonists with TM3 side of the ligand-binding pocket rather than TM6/7 side. In contrast, morphine and fentanyl form dual interactions with both TM3 and TM6/7 regions. Mutations at the TM6/7 interface abolish arrestin recruitment of muOR promoted by morphine and fentanyl. Ligands designed to reduce TM6/7 interactions display preferential G protein signaling. Our results provide crucial insights into fentanyl recognition and signaling of muOR, which may facilitate rational design of next-generation analgesics.

Molecular recognition of morphine and fentanyl by the human mu-opioid receptor.,Zhuang Y, Wang Y, He B, He X, Zhou XE, Guo S, Rao Q, Yang J, Liu J, Zhou Q, Wang X, Liu M, Liu W, Jiang X, Yang D, Jiang H, Shen J, Melcher K, Chen H, Jiang Y, Cheng X, Wang MW, Xie X, Xu HE Cell. 2022 Nov 10;185(23):4361-4375.e19. doi: 10.1016/j.cell.2022.09.041. PMID:36368306<ref>PMID:36368306</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8efq" style="background-color:#fffaf0;"></div>

==See Also==
*[[Opioid receptor|Opioid receptor]]
*[[Transducin 3D structures|Transducin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bos taurus]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Synthetic construct]]
[[Category: Chen X]]
[[Category: Guo S]]
[[Category: He B]]
[[Category: He X]]
[[Category: Jiang H]]
[[Category: Jiang X]]
[[Category: Jiang Y]]
[[Category: Liu J]]
[[Category: Liu W]]
[[Category: Melcher K]]
[[Category: Rao Q]]
[[Category: Shen J]]
[[Category: Wang M]]
[[Category: Wang X]]
[[Category: Wang Y]]
[[Category: Xie X]]
[[Category: Xu HE]]
[[Category: Yang D]]
[[Category: Zhou Q]]
[[Category: Zhou XE]]
[[Category: Zhuang Y]]