Fingerprinting G-protein-coupled receptors

Recently we reported the design of a discriminating fingerprintfor rhodopsin-like G-protein-coupled receptors (GPCRs). Thefingerprint encodes the seven putative membrane-spanning motifsand was potently diagnostic of all GPCRs (52 in all) in version8.1 of the OWL composite sequence database, readily distinguishingthem from all other integral membrane proteins. With a 3-foldincrease in the size of OWL, the fingerprint has been updatedand now finds 332 receptors that match all the motifs. The situation,however, has grown in complexity: 61 sequences make imperfectmatches with the fingerprint, yielding a total of 393 ‘hits’.The bulk of the partial hits are olfactory receptors: theseappear to fall into discrete subfamilies in which one or moreof the transmembrane motifs are either poorly matched or arenot matched at all. These results are supported by preliminaryphylogenetic analyses, which show the olfactory and variousother partial matches clustering away from the main body oftrue hits. The approach has provided a powerful diagnostic toolfor identifying GPCRs, and results are consistent with previousobservations that the pheromone, cAMP and secretin-like receptorsbelong to separate families-these bear their own unique sequencefingerprints by which they may be distinguished from the rhodopsin-likesuperfamily