26xh: Difference between revisions
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The | ==Cryo-EM structure of Maleic Acid bound OXGR1-Gq complex== | ||
<StructureSection load='26xh' size='340' side='right'caption='[[26xh]], [[Resolution|resolution]] 2.82Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[26xh]] is a 6 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=26XH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=26XH 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]] 2.82Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MAE:MALEIC+ACID'>MAE</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=26xh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=26xh OCA], [https://pdbe.org/26xh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=26xh RCSB], [https://www.ebi.ac.uk/pdbsum/26xh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=26xh ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/GBG2_HUMAN GBG2_HUMAN] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction (By similarity). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The ability of cells to sense and respond to metabolic signals is fundamental to life, yet the molecular mechanisms underlying metabolite surveillance remain incompletely understood. Here, we elucidate the structural basis of metabolite recognition by OXGR1, a G Protein-Coupled Receptor (GPCR) that senses key intermediates in the tricarboxylic acid (TCA) cycle. Using cryo-electron microscopy, we determined cryo-EM structures of OXGR1 bound to alpha-ketoglutarate (AKG), itaconate (ITA), and structurally related metabolites succinate (SUC) and maleate (MA). These structures reveal a positively charged binding pocket and an extensive hydrogen-bond network that mediate selective recognition of dicarboxylic acids. In addition, we identify a distinct arrangement of hydrophobic residues that modulates ligand potency and selectivity. Mutational analysis and molecular dynamics simulations further demonstrate that noncanonical micro-switch motifs, including FRY and NLxxY, are essential for ligand recognition and receptor activation. Comparative structural and evolutionary analyses indicate that these mechanisms are conserved across species, underscoring the critical role of OXGR1 in maintaining metabolic homeostasis. Together, our findings define a mechanistic framework for metabolite sensing by OXGR1 and provide a framework for therapeutic modulation of metabolic and inflammatory diseases. | |||
Molecular architecture of OXGR1 reveals an evolutionary conserved mechanisms for metabolite surveillance.,Zhang X, Lu Y, He X, Guo S, Li C, Wang Y, Gao Y, Yao J, Yuan Q, Tang Y, Hu J, Hu W, Luo Z, Wu K, Wang Y, Yin W, Xie X, Xu HE, Liu H EMBO J. 2026 Jun 3. doi: 10.1038/s44318-026-00823-y. PMID:42236546<ref>PMID:42236546</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 26xh" style="background-color:#fffaf0;"></div> | ||
[[Category: Liu | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Lama glama]] | |||
[[Category: Large Structures]] | |||
[[Category: Liu H]] | |||
[[Category: Zhang X]] | |||