Structural insights into the inactive and active states of the A3 adenosine receptor

Adenosine receptors (ARs) represent attractive therapeutic targets for multiple conditions. The molecular details that underlie their mechanism of action are limited by the lack of structural information on A3AR ligand binding and activation of the receptor. We extend knowledge of A3AR structure and activation, through application of cryo-EM to analyse the structure and ligand interaction networks of A3AR bound with different ligands. These structures provide insights into the activation mechanism of A3AR that can guide the rational design of A3AR ligands and broaden a framework for understanding the ligand binding, activation, and signalling mechanism of ARs.