Fig. 1: The variable topology of the G protein-coupled receptor (GPCR) autoproteolysis inducing (GAIN) domain.
From: Generic residue numbering of the GAIN domain of adhesion GPCRs
a adhesion GPCR topology with the N-terminal extracellular region composed of various extracellular domains (ECDs) and the GAIN domain directly N-terminal of the seven-transmembrane domain (TM). The GAIN domain is comprised of subdomains A and B, with the tethered agonist (TA) as the most C-terminal β-strand. The GAIN domain is frequently preceded by a hormone receptor motif (HRM) domain of unknown function. b the GAIN domain is composed of two subdomains, with subdomain A (blue) comprised of 2–6 α-helices with conservation decreasing toward the N-terminal boundary. The β-sandwich subdomain B (orange) is composed of 13–14 β-strands with a conserved autoproteolytic cleavage triad (GPS) of sequence HL | T/S (red triangle: cleavage site), followed by the tethered agonist (TA, yellow). c the GAIN domain of rat ADGRL1 (PDB ID: 4DLQ9) shows all hallmarks of the GAIN domain.
