Figure 5.
Overall view of the shark A0 homology model compared with human A2a and A1 receptors (PDB codes 2ydv and 6d9h). The approximate position of the hydrophobic stretch of the lipid bilayer is depicted with lines separated by ∼35 Å using conserved aromatic side chains as fiducials (17). A striking feature of shark A0 compared with the more specialized adenosine receptors (ADORs) is an abbreviated extracellular loop 2 (ECL2, labeled) and the relatively low profile that the A0 receptor presents to the extracellular milieu. Multiple sequence alignment of all known and putative receptor orthologs (see Supplemental Figs. S9 and S10) reveals that an abbreviated ECL2 appears to be a unique feature of ancestral ADORs.