8h8j: Difference between revisions

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-'''Unreleased structure'''
-The entry 8h8j is ON HOLD
+==Lodoxamide-bound GPR35 in complex with G13==
+<StructureSection load='8h8j' size='340' side='right'caption='[[8h8j]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8h8j]] 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=8H8J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8H8J 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]] 3.2&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=WYB:2-[[3-(carboxycarbonylamino)-2-chloranyl-5-cyano-phenyl]amino]-2-oxidanylidene-ethanoic+acid'>WYB</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=8h8j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8h8j OCA], [https://pdbe.org/8h8j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8h8j RCSB], [https://www.ebi.ac.uk/pdbsum/8h8j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8h8j ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/GNA13_HUMAN GNA13_HUMAN] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems (PubMed:15240885, PubMed:16705036, PubMed:16787920, PubMed:27084452). Activates effector molecule RhoA by binding and activating RhoGEFs (ARHGEF1/p115RhoGEF, ARHGEF11/PDZ-RhoGEF and ARHGEF12/LARG) (PubMed:12515866, PubMed:15240885). GNA13-dependent Rho signaling subsequently regulates transcription factor AP-1 (activating protein-1) (By similarity). Promotes tumor cell invasion and metastasis by activating RhoA/ROCK signaling pathway (PubMed:16705036, PubMed:16787920, PubMed:27084452). Inhibits CDH1-mediated cell adhesion in process independent from Rho activation (PubMed:11976333).[UniProtKB:P27601]<ref>PMID:11976333</ref> <ref>PMID:12515866</ref> <ref>PMID:15240885</ref> <ref>PMID:16705036</ref> <ref>PMID:16787920</ref> <ref>PMID:27084452</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Endogenous ions play important roles in the function and pharmacology of G protein-coupled receptors (GPCRs) with limited atomic evidence. In addition, compared with G protein subtypes G(s), G(i/o), and G(q/11), insufficient structural evidence is accessible to understand the coupling mechanism of G(12/13) protein by GPCRs. Orphan receptor GPR35, which is predominantly expressed in the gastrointestinal tract and is closely related to inflammatory bowel diseases (IBDs), stands out as a prototypical receptor for investigating ionic modulation and G(13) coupling. Here we report a cryo-electron microscopy structure of G(13)-coupled GPR35 bound to an anti-allergic drug, lodoxamide. This structure reveals a novel divalent cation coordination site and a unique ionic regulatory mode of GPR35 and also presents a highly positively charged binding pocket and the complementary electrostatic ligand recognition mode, which explain the promiscuity of acidic ligand binding by GPR35. Structural comparison of the GPR35-G(13) complex with other G protein subtypes-coupled GPCRs reveals a notable movement of the C-terminus of alpha5 helix of the Galpha(13) subunit towards the receptor core and the least outward displacement of the cytoplasmic end of GPR35 TM6. A featured 'methionine pocket' contributes to the G(13) coupling by GPR35. Together, our findings provide a structural basis for divalent cation modulation, ligand recognition, and subsequent G(13) protein coupling of GPR35 and offer a new opportunity for designing GPR35-targeted drugs for the treatment of IBDs.
-Authors: Yuan, Q., Duan, J., Liu, Q., Xu, H.E., Jiang, Y.
+Insights into divalent cation regulation and G(13)-coupling of orphan receptor GPR35.,Duan J, Liu Q, Yuan Q, Ji Y, Zhu S, Tan Y, He X, Xu Y, Shi J, Cheng X, Jiang H, Eric Xu H, Jiang Y Cell Discov. 2022 Dec 21;8(1):135. doi: 10.1038/s41421-022-00499-8. PMID:36543774<ref>PMID:36543774</ref>
-Description: Lodoxamide-bound GPR35 in complex with G13
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Xu, H.E]]
+<div class="pdbe-citations 8h8j" style="background-color:#fffaf0;"></div>
-[[Category: Duan, J]]
-[[Category: Liu, Q]]
+==See Also==
-[[Category: Yuan, Q]]
+*[[Transducin 3D structures|Transducin 3D structures]]
-[[Category: Jiang, Y]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Mus musculus]]
+[[Category: Duan J]]
+[[Category: Jiang Y]]
+[[Category: Liu Q]]
+[[Category: Xu HE]]
+[[Category: Yuan Q]]