7ejx: Difference between revisions
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==== | ==Structure of the GPR88-Gi1 signaling complex bound to a synthetic ligand== | ||
<StructureSection load='7ejx' size='340' side='right'caption='[[7ejx]]' scene=''> | <StructureSection load='7ejx' size='340' side='right'caption='[[7ejx]], [[Resolution|resolution]] 2.40Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[7ejx]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7EJX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EJX FirstGlance]. <br> | ||
</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=7ejx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ejx OCA], [https://pdbe.org/7ejx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ejx RCSB], [https://www.ebi.ac.uk/pdbsum/7ejx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ejx ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=J5F:(1R,2R)-N-[(2S,3S)-2-azanyl-3-methyl-pentyl]-N-[4-(4-propylphenyl)phenyl]-2-pyridin-2-yl-cyclopropane-1-carboxamide'>J5F</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=7ejx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ejx OCA], [https://pdbe.org/7ejx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ejx RCSB], [https://www.ebi.ac.uk/pdbsum/7ejx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ejx ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Disease == | |||
[https://www.uniprot.org/uniprot/GPR88_HUMAN GPR88_HUMAN] The disease is caused by variants affecting the gene represented in this entry. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/GPR88_HUMAN GPR88_HUMAN] Probable G-protein coupled receptor implicated in a large repertoire of behavioral responses that engage motor activities, spatial learning, and emotional processing. May play a role in the regulation of cognitive and motor function.[UniProtKB:Q9EPB7][UniProtKB:Q9ESP4] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
GPR88 is an orphan class A G-protein-coupled receptor that is highly expressed in the striatum and regulates diverse brain and behavioral functions. Here we present cryo-EM structures of the human GPR88-Gi1 signaling complex with or without a synthetic agonist (1R, 2R)-2-PCCA. We show that (1R, 2R)-2-PCCA is an allosteric modulator binding to a herein identified pocket formed by the cytoplasmic ends of transmembrane segments 5, 6, and the extreme C terminus of the alpha5 helix of Gi1. We also identify an electron density in the extracellular orthosteric site that may represent a putative endogenous ligand of GPR88. These structures, together with mutagenesis studies and an inactive state model obtained from metadynamics simulations, reveal a unique activation mechanism for GPR88 with a set of distinctive structure features and a water-mediated polar network. Overall, our results provide a structural framework for understanding the ligand binding, activation and signaling mechanism of GPR88, and will facilitate the innovative drug discovery for neuropsychiatric disorders and for deorphanization of this receptor. | |||
Activation and allosteric regulation of the orphan GPR88-Gi1 signaling complex.,Chen G, Xu J, Inoue A, Schmidt MF, Bai C, Lu Q, Gmeiner P, Liu Z, Du Y Nat Commun. 2022 May 2;13(1):2375. doi: 10.1038/s41467-022-30081-5. PMID:35501348<ref>PMID:35501348</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7ejx" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Transducin 3D structures|Transducin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Z | [[Category: Mus musculus]] | ||
[[Category: Chen G]] | |||
[[Category: Du Y]] | |||
[[Category: Liu Z]] | |||
[[Category: Xu J]] | |||
Latest revision as of 06:22, 26 October 2022
Structure of the GPR88-Gi1 signaling complex bound to a synthetic ligand
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