26xh

Cryo-EM structure of Maleic Acid bound OXGR1-Gq complex

spinqualitylabelsall models 26xh, resolution 2.82Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 26xh is a 6 chain structure with sequence from Homo sapiens and Lama glama. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.82Å Ligands: MAE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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). 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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