9vmp | pdb_00009vmp

Cryo-EM structure of the A-1-OXGR1-Gq complex

spinqualitylabelsall models 9vmp, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9vmp is a 5 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.5Å Ligands: A1E2R Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GBB1_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. Publication Abstract from PubMed Rosacea, an inflammatory skin disorder, poses a dilemma owing to limited effectiveness of treatments for pathological vasodilation-mediated erythema. Here, we identify oxoglutaric acid (alpha-KG) as a rosacea-associated metabolite elevated in patients and correlated with erythema severity. Exogenous alpha-KG administration ameliorates rosacea-like manifestations in murine models. Mechanistically, alpha-KG activates OXGR1, a vascular smooth muscle cell (VSMC)-enriched G protein-coupled receptor (GPCR) to induce Gq signaling and enhance MYL9 phosphorylation, promoting VSMC contraction and limiting vasodilation. Cryo-electron microscopy (cryo-EM) structures of OXGR1-Gq complexes bound to alpha-KG or itaconate reveal a specific bipartite-acid pocket recognizing its endogenous agonist and an activation mechanism distinct from classical GPCRs. Building on these structures, we developed A-1, a synthetic selective OXGR1 agonist that mitigates erythema and inflammation with efficacy comparable to first-line therapy while offering enhanced safety in rosacea-like models. These findings link a metabolite to vascular dysfunction and nominate OXGR1 agonism for precision treatment of erythema and vascular disorders. Metabolite-gated vascular contractility switch: OXGR1 activation mechanism enables agonist therapy for rosacea erythema.,Xiao W, Zhu Y, Tang X, Zhu K, Zhang W, Chen M, Cai K, Xu S, Wu Z, Wang M, Liu J, Long L, Tan Z, Wu A, Zhou S, Zhao Z, Tang Y, Huang Y, Wang B, Liu F, Wang Q, Yang F, Jian D, Shi W, Xie H, Chen X, Guo L, Deng Z, Sun J, Li J Cell. 2026 Mar 5:S0092-8674(26)00164-9. doi: 10.1016/j.cell.2026.01.036. PMID:41791372 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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