Structural Mapping of Adenosine Receptor Mutations: Ligand Binding and Signaling Mechanisms

Abstract

The four adenosine receptors (ARs), A₁, A_2A, A_2B, and A₃, constitute a subfamily of G protein-coupled receptors (GPCRs) with exceptional foundations for structure-based ligand design. The vast amount of mutagenesis data, accumulated in the literature since the 1990s, has been recently supplemented with structural information, currently consisting of several inactive and active structures of the A_2A and inactive conformations of the A₁ ARs. We provide the first integrated view of the pharmacological, biochemical, and structural data available for this receptor family, by mapping onto the relevant crystal structures all site-directed mutagenesis data, curated and deposited at the GPCR database (available through http://www.gpcrdb.org). This analysis provides novel insights into ligand binding, allosteric modulation, and signaling of the AR family.

Keywords: G protein-coupled receptor; adenosine receptor; chemical modulation; mutagenesis.