7yu8

Human Lysophosphatidic Acid Receptor 1-Gi complex bound to ONO-0740556, state4

spinqualitylabelsall models 7yu8, resolution 5.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7yu8 is a 5 chain structure with sequence from Bos taurus, Homo sapiens, Mus musculus and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 5.6Å Ligands: K6L Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GBB1_RAT 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 Lysophosphatidic acid receptor 1 (LPA(1)) is one of the six G protein-coupled receptors activated by the bioactive lipid, lysophosphatidic acid (LPA). LPA(1) is a drug target for various diseases, including cancer, inflammation, and neuropathic pain. Notably, LPA(1) agonists have potential therapeutic value for obesity and urinary incontinence. Here, we report a cryo-electron microscopy structure of the active human LPA(1)-G(i) complex bound to ONO-0740556, an LPA analog with more potent activity against LPA(1). Our structure elucidated the details of the agonist binding mode and receptor activation mechanism mediated by rearrangements of transmembrane segment 7 and the central hydrophobic core. A structural comparison of LPA(1) and other phylogenetically-related lipid-sensing GPCRs identified the structural determinants for lipid preference of LPA(1). Moreover, we characterized the structural polymorphisms at the receptor-G-protein interface, which potentially reflect the G-protein dissociation process. Our study provides insights into the detailed mechanism of LPA(1) binding to agonists and paves the way toward the design of drug-like agonists targeting LPA(1). Structure of the active G(i)-coupled human lysophosphatidic acid receptor 1 complexed with a potent agonist.,Akasaka H, Tanaka T, Sano FK, Matsuzaki Y, Shihoya W, Nureki O Nat Commun. 2022 Sep 15;13(1):5417. doi: 10.1038/s41467-022-33121-2. PMID:36109516 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Lysophosphatidic acid receptor Transducin 3D structures

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