View source for 8kgk


==Cryo-EM structure of the GPR61-Gs complex==
<StructureSection load='8kgk' size='340' side='right'caption='[[8kgk]], [[Resolution|resolution]] 3.16&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8kgk]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8KGK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8KGK 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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8kgk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8kgk OCA], [https://pdbe.org/8kgk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8kgk RCSB], [https://www.ebi.ac.uk/pdbsum/8kgk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8kgk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GPR61_HUMAN GPR61_HUMAN] Orphan G-protein coupled receptor. Constitutively activates the G(s)-alpha/cAMP signaling pathway (PubMed:28827538). Shows a reciprocal regulatory interaction with the melatonin receptor MTNR1B most likely through receptor heteromerization (PubMed:28827538). May be involved in the regulation of food intake and body weight (By similarity).[UniProtKB:Q8C010]<ref>PMID:28827538</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Many orphan G protein-coupled receptors (GPCRs) remain understudied because their endogenous ligands are unknown. Here, we show that a group of class A/rhodopsin-like orphan GPCRs including GPR61, GPR161 and GPR174 increase the cAMP level similarly to fully activated D1 dopamine receptor (D1R). We report cryo-electron microscopy structures of the GPR61âG(s), GPR161âG(s) and GPR174âG(s) complexes without any exogenous ligands. The GPR174 structure reveals that endogenous lysophosphatidylserine (lysoPS) is copurified. While GPR174 fails to respond to exogenous lysoPS, likely owing to its maximal activation by the endogenous ligand, GPR174 mutants with lower ligand binding affinities can be specifically activated by lysoPS but not other lipids, in a dose-dependent manner. Moreover, GPR174 adopts a non-canonical G(s) coupling mode. The structures of GPR161 and GPR61 reveal that the second extracellular loop (ECL2) penetrates into the orthosteric pocket, possibly contributing to constitutive activity. Our work definitively confirms lysoPS as an endogenous GPR174 ligand and suggests that high constitutive activity of some orphan GPCRs could be accounted for by their having naturally abundant ligands.

Specific binding of GPR174 by endogenous lysophosphatidylserine leads to high constitutive G(s) signaling.,Nie Y, Qiu Z, Chen S, Chen Z, Song X, Ma Y, Huang N, Cyster JG, Zheng S Nat Commun. 2023 Sep 22;14(1):5901. doi: 10.1038/s41467-023-41654-3. PMID:37737235<ref>PMID:37737235</ref>

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

==See Also==
*[[Transducin 3D structures|Transducin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Lama glama]]
[[Category: Large Structures]]
[[Category: Nie Y]]
[[Category: Qiu Z]]
[[Category: Zheng S]]