GPCRdb: the G protein-coupled receptor database - an introduction.

GPCRs make up the largest family of human membrane proteins and of drug targets. Recent advances in GPCR pharmacology and crystallography have shed new light on signal transduction, allosteric modulation and biased signalling, translating into new mechanisms and principles for drug design. The GPCR database, GPCRdb, has served the community for over 20 years and has recently been extended to include a more multidisciplinary audience. This review is intended to introduce new users to the services in GPCRdb, which meets three overall purposes: firstly, to provide reference data in an integrated, annotated and structured fashion, with a focus on sequences, structures, single-point mutations and ligand interactions. Secondly, to equip the community with a suite of web tools for swift analysis of structures, sequence similarities, receptor relationships, and ligand target profiles. Thirdly, to facilitate dissemination through interactive diagrams of, for example, receptor residue topologies, phylogenetic relationships and crystal structure statistics. Herein, these services are described for the first time; visitors and guides are provided with good practices for their utilization. Finally, we describe complementary databases cross-referenced by GPCRdb and web servers with corresponding functionality.

High species variation within the repertoire of trace amine receptors.

Using a variety of search strategies, we obtained the complete or nearly complete repertoire of trace amine receptors from humans, mice, rats, zebrafish, pufferfish, and a number of invertebrates. We found that the number of functional receptors varies from 5 to 50 in each genome, showing that this family of GPCRs has a very dynamic gene repertoire. We show that the previously cloned and characterized GPCRs from insects and mollusks are more closely related to mammalian serotonin, dopamine, and adrenalin receptors than to mammalian TA receptors. This suggests that the ability to bind TAs has arisen independently in different developmental lineages.