9v6t: Difference between revisions

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~~'''Unreleased structure'''~~

~~The entry~~ 9v6t is ~~ON HOLD until Paper~~ Publication

==Cryo-EM structure of the GLPG1205-bound GPR84 receptor==

== Structural highlights ==

<table><tr><td colspan='2'>[[9v6t]] 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=9V6T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9V6T 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]] 3.5Å</td></tr>

<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1L93:9-(2-cyclopropylethynyl)-2-[[(2~{S})-1,4-dioxan-2-yl]methoxy]-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one'>A1L93</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=9v6t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9v6t OCA], [https://pdbe.org/9v6t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9v6t RCSB], [https://www.ebi.ac.uk/pdbsum/9v6t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9v6t ProSAT]</span></td></tr>

</table>

== Function ==

[https://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX] Electron-transport protein of unknown function.

== Publication Abstract from PubMed ==

G-protein-coupled receptor 84 (GPR84) is an orphan class A GPCR selectively activated by medium chain fatty acids and highly expressed in immune cells, where it modulates pro-inflammatory signaling. The structural basis of GPR84 inactivation and antagonism has remained unclear, limiting the rational design of pathway-selective modulators despite its clinical relevance in metabolic inflammation and fibrotic diseases. Here, we report cryo-electron microscopy structures of human GPR84 in inactive and active states. The 3.5 A inactive structure bound to the antagonist GLPG1205 reveals a lid-like conformation of extracellular loop 2 and an inward reorientation of Arg172, with the antagonist head group blocking the allosteric sodium-binding site. Molecular dynamics simulations further support these findings, identifying an aberrant TM5, TM6 lateral entry gate. By contrast, the 3.17 A agonist ZQ-16, Galphai complex, shows a rearranged toggle switch and comparative analyses highlight extracellular loop 2 conformational plasticity. Immune functional assays in THP-1 cells demonstrated that ZQ-16 elicited GPR84-dependent activation and cytokine production, which were effectively abrogated by GLPG1205. Mutagenesis combined with functional assays validates key ligand interactions, providing a framework for the rational design of pathway selective GPR84 modulators.

~~Authors:~~ Choi, M.K.~~, Cho, H~~.S.

Pharmacological modulation of GPR84 revealed by dual states structures and immune functional assays.,Choi MK, Park DJ, Kim P, Choi HS, Myung S, Yoo Y, Chang N, Yoon GY, Kang HJ, Ha SJ, Cho HS Exp Mol Med. 2026 Sep 10. doi: 10.1038/s12276-026-01841-w. PMID:42722702<ref>PMID:42722702</ref>

~~Description: Cryo-EM structure~~ of the ~~GLPG1205~~-~~bound GPR84 receptor~~

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

[[Category: ~~Unreleased~~ Structures]]

</div>

[[Category: ~~Choi, M.K~~]]

[[Category: ~~Cho, H.S~~]]

== References ==

__TOC__

</StructureSection>

[[Category: Homo sapiens]]

[[Category: Large Structures]]

[[Category: Cho HS]]

[[Category: Choi MK]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9v6t is ON HOLD  until Paper Publication
+==Cryo-EM structure of the GLPG1205-bound GPR84 receptor==
+<StructureSection load='9v6t' size='340' side='right'caption='[[9v6t]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9v6t]] 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=9V6T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9V6T 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]] 3.5&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1L93:9-(2-cyclopropylethynyl)-2-[[(2~{S})-1,4-dioxan-2-yl]methoxy]-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one'>A1L93</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=9v6t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9v6t OCA], [https://pdbe.org/9v6t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9v6t RCSB], [https://www.ebi.ac.uk/pdbsum/9v6t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9v6t ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX] Electron-transport protein of unknown function.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+G-protein-coupled receptor 84 (GPR84) is an orphan class A GPCR selectively activated by medium chain fatty acids and highly expressed in immune cells, where it modulates pro-inflammatory signaling. The structural basis of GPR84 inactivation and antagonism has remained unclear, limiting the rational design of pathway-selective modulators despite its clinical relevance in metabolic inflammation and fibrotic diseases. Here, we report cryo-electron microscopy structures of human GPR84 in inactive and active states. The 3.5 A inactive structure bound to the antagonist GLPG1205 reveals a lid-like conformation of extracellular loop 2 and an inward reorientation of Arg172, with the antagonist head group blocking the allosteric sodium-binding site. Molecular dynamics simulations further support these findings, identifying an aberrant TM5, TM6 lateral entry gate. By contrast, the 3.17 A agonist ZQ-16, Galphai complex, shows a rearranged toggle switch and comparative analyses highlight extracellular loop 2 conformational plasticity. Immune functional assays in THP-1 cells demonstrated that ZQ-16 elicited GPR84-dependent activation and cytokine production, which were effectively abrogated by GLPG1205. Mutagenesis combined with functional assays validates key ligand interactions, providing a framework for the rational design of pathway selective GPR84 modulators.
-Authors: Choi, M.K., Cho, H.S.
+Pharmacological modulation of GPR84 revealed by dual states structures and immune functional assays.,Choi MK, Park DJ, Kim P, Choi HS, Myung S, Yoo Y, Chang N, Yoon GY, Kang HJ, Ha SJ, Cho HS Exp Mol Med. 2026 Sep 10. doi: 10.1038/s12276-026-01841-w. PMID:42722702<ref>PMID:42722702</ref>
-Description: Cryo-EM structure of the GLPG1205-bound GPR84 receptor
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Choi, M.K]]
+<div class="pdbe-citations 9v6t" style="background-color:#fffaf0;"></div>
-[[Category: Cho, H.S]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Cho HS]]
+[[Category: Choi MK]]