8x16

Cryo-EM structure of adenosine receptor A3AR bound to CF101

spinqualitylabelsall models 8x16, resolution 3.29Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8x16 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 3.29Å Ligands: Q8L 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 The adenosine A(3) receptor (A(3)AR), a key member of the G protein-coupled receptor family, is a promising therapeutic target for inflammatory and cancerous conditions. The selective A(3)AR agonists, CF101 and CF102, are clinically significant, yet their recognition mechanisms remained elusive. Here we report the cryogenic electron microscopy structures of the full-length human A(3)AR bound to CF101 and CF102 with heterotrimeric G(i) protein in complex at 3.3-3.2 A resolution. These agonists reside in the orthosteric pocket, forming conserved interactions via their adenine moieties, while their 3-iodobenzyl groups exhibit distinct orientations. Functional assays reveal the critical role of extracellular loop 3 in A(3)AR's ligand selectivity and receptor activation. Key mutations, including His(3.37), Ser(5.42), and Ser(6.52), in a unique sub-pocket of A(3)AR, significantly impact receptor activation. Comparative analysis with the inactive A(2A)AR structure highlights a conserved receptor activation mechanism. Our findings provide comprehensive insights into the molecular recognition and signaling of A(3)AR, paving the way for designing subtype-selective adenosine receptor ligands. Cryo-EM structures of adenosine receptor A(3)AR bound to selective agonists.,Cai H, Guo S, Xu Y, Sun J, Li J, Xia Z, Jiang Y, Xie X, Xu HE Nat Commun. 2024 Apr 16;15(1):3252. doi: 10.1038/s41467-024-47207-6. PMID:38627384 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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