8X16
Cryo-EM structure of adenosine receptor A3AR bound to CF101
Summary for 8X16
Entry DOI | 10.2210/pdb8x16/pdb |
EMDB information | 37985 |
Descriptor | Adenosine receptor A3, Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, ... (6 entities in total) |
Functional Keywords | gpcr, adenosine a3 receptor, ligand selectivity, cf101, membrane protein, membrane protein-immune system complex, membrane protein/immune system |
Biological source | Homo sapiens (human) More |
Total number of polymer chains | 5 |
Total formula weight | 149223.75 |
Authors | |
Primary citation | Cai, H.,Guo, S.,Xu, Y.,Sun, J.,Li, J.,Xia, Z.,Jiang, Y.,Xie, X.,Xu, H.E. Cryo-EM structures of adenosine receptor A 3 AR bound to selective agonists. Nat Commun, 15:3252-3252, 2024 Cited by PubMed Abstract: The adenosine A receptor (AAR), a key member of the G protein-coupled receptor family, is a promising therapeutic target for inflammatory and cancerous conditions. The selective AAR 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 AAR bound to CF101 and CF102 with heterotrimeric G protein in complex at 3.3-3.2 Å 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 AAR's ligand selectivity and receptor activation. Key mutations, including His, Ser, and Ser, in a unique sub-pocket of AAR, significantly impact receptor activation. Comparative analysis with the inactive AAR structure highlights a conserved receptor activation mechanism. Our findings provide comprehensive insights into the molecular recognition and signaling of AAR, paving the way for designing subtype-selective adenosine receptor ligands. PubMed: 38627384DOI: 10.1038/s41467-024-47207-6 PDB entries with the same primary citation |
Experimental method | ELECTRON MICROSCOPY (3.29 Å) |
Structure validation
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