8X17

Cryo-EM structure of adenosine receptor A3AR bound to CF102

8X17 の概要

• エントリーDOI: 10.2210/pdb8x17/pdb
• EMDBエントリー: 37986
• 分子名称: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Adenosine receptor A3, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (6 entities in total)
• 機能のキーワード: gpcr, adenosine a3 receptor, ligand selectivity, cf102, membrane protein
• 由来する生物種: Rattus norvegicus (Norway rat); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 149258.19

構造登録者

Cai, H.,Xu, Y.,Xu, H.E. (登録日: 2023-11-06, 公開日: 2024-04-24, 最終更新日: 2024-11-13)

主引用文献

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

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: 38627384
DOI: 10.1038/s41467-024-47207-6

実験手法

ELECTRON MICROSCOPY (3.19 Å)