Generic residue numbering of the GAIN domain of adhesion GPCRs.

ABSTRACT: The GPCR autoproteolysis inducing (GAIN) domain is an ancient protein fold ubiquitous in adhesion G protein-coupled receptors (aGPCR). It contains a tethered agonist necessary and sufficient for receptor activation. The GAIN domain is a hotspot for pathological mutations. However, the low primary sequence conservation of GAIN domains has thus far hindered the knowledge transfer across different GAIN domains in human receptors as well as species orthologs. Here, we present a scheme for generic residue numbering of GAIN domains, based on structural alignments of over 14,000 modeled GAIN domain structures. This scheme is implemented in the GPCR database (GPCRdb) and elucidates the domain topology across different aGPCRs and their homologs in a large panel of species. We identify conservation

SUBMITTER: Seufert F 

PROVIDER: S-EPMC11697300 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature