Fig. 2: GAIN domain helix and strand architecture of human adhesion G protein-coupled receptors (aGPCRs) and conservation across orthologs.
From: Generic residue numbering of the GAIN domain of adhesion GPCRs
a Example chimeric GAIN domain structure showing all six helices, 14 strands, and the GPCR proteolytic site (GPS) on its topology, a red asterisk marks the autoproteolytic cleavage site N-terminal of the tethered agonist (S14). b each row represents all orthologs in the UniProtKB database that have a GAIN domain for each receptor, where individual elements are highlighted by occupancy (blue: subdomain A helices, orange: subdomain B strands), higher color intensity represents a higher conservation of the element within the group of orthologs. White circles denote elements that are not present in the corresponding human aGPCR GAIN domain (ADGRA1 without GAIN; ADGRE4 is a pseudogene in humans). Other receptors (red label) are aGPCRs without a receptor ortholog in humans. A set of 2872 polycystic kidney disease-type proteins (PKD, green label) have GAIN domains, which were matched against the set of aGPCR templates, matching well with an additional beta-sandwich subdomain between extended S9 and S10. c residue conservation for residues indexed with the GAIN-GRN for subdomain A (shades of blue) and subdomain B (shades of orange), with 14435 GAIN domains as the underlying number of GAIN domains. Unindexed residues are colored green.
