Cryo-EM structures of adenosine receptor A₃AR bound to selective agonists.

ABSTRACT: The adenosine A₃ receptor (A₃AR), a key member of the G protein-coupled receptor family, is a promising therapeutic target for inflammatory and cancerous conditions. The selective A₃AR 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 A₃AR bound to CF101 and CF102 with heterotrimeric G_i 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 A₃AR's ligand select

SUBMITTER: Cai H 

PROVIDER: S-EPMC11021478 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature