View source for 7ewp


==Cryo-EM structure of human GPR158 in complex with RGS7-Gbeta5 in a 2:1:1 ratio==
<StructureSection load='7ewp' size='340' side='right'caption='[[7ewp]], [[Resolution|resolution]] 4.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7ewp]] 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=7EWP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EWP 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]] 4.3&#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=7ewp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ewp OCA], [https://pdbe.org/7ewp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ewp RCSB], [https://www.ebi.ac.uk/pdbsum/7ewp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ewp ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/GNB5_HUMAN GNB5_HUMAN] GNB5-related intellectual disability-cardiac arrhythmia syndrome. The disease is caused by variants affecting the gene represented in this entry.  The disease is caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/GNB5_HUMAN GNB5_HUMAN] Enhances GTPase-activating protein (GAP) activity of regulator of G protein signaling (RGS) proteins, such as RGS7 and RGS9, hence involved in the termination of the signaling initiated by the G protein coupled receptors (GPCRs) by accelerating the GTP hydrolysis on the G-alpha subunits, thereby promoting their inactivation (PubMed:27677260). Increases RGS7 GTPase-activating protein (GAP) activity, thereby regulating mood and cognition (By similarity). Increases RGS9 GTPase-activating protein (GAP) activity, hence contributes to the deactivation of G protein signaling initiated by D(2) dopamine receptors (PubMed:27677260). May play an important role in neuronal signaling, including in the parasympathetic, but not sympathetic, control of heart rate (By similarity).[UniProtKB:A1L271][UniProtKB:P62881]<ref>PMID:27677260</ref> 
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== Publication Abstract from PubMed ==
GPR158, a class C orphan GPCR, functions in cognition, stress-induced mood control, and synaptic development. Among class C GPCRs, GPR158 is unique as it lacks a Venus flytrap-fold ligand-binding domain and terminates Galphai/o protein signaling through the RGS7-Gbeta5 heterodimer. Here, we report the cryo-EM structures of GPR158 alone and in complex with one or two RGS7-Gbeta5 heterodimers. GPR158 dimerizes through Per-Arnt-Sim-fold extracellular and transmembrane (TM) domains connected by an epidermal growth factor-like linker. The TM domain (TMD) reflects both inactive and active states of other class C GPCRs: a compact intracellular TMD, conformations of the two intracellular loops (ICLs) and the TMD interface formed by TM4/5. The ICL2, ICL3, TM3, and first helix of the cytoplasmic coiled-coil provide a platform for the DHEX domain of one RGS7 and the second helix recruits another RGS7. The unique features of the RGS7-binding site underlie the selectivity of GPR158 for RGS7.

Structure of the class C orphan GPCR GPR158 in complex with RGS7-Gbeta5.,Jeong E, Kim Y, Jeong J, Cho Y Nat Commun. 2021 Nov 23;12(1):6805. doi: 10.1038/s41467-021-27147-1. PMID:34815401<ref>PMID:34815401</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7ewp" style="background-color:#fffaf0;"></div>

==See Also==
*[[Regulator of G-protein signaling 3D structures|Regulator of G-protein signaling 3D structures]]
*[[Transducin 3D structures|Transducin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cho Y]]
[[Category: Jeong E]]
[[Category: Jeong J]]
[[Category: Kim Y]]