FINGERPRINTING G-PROTEIN-COUPLED RECEPTORS

Recently we reported the design of a discriminating fingerprint for rh odopsin-like G-protein-coupled receptors (GPCRs). The fingerprint enco des the seven putative membrane-spanning moths and was potently diagno stic of all GPCRs (52 in all) in version 8.1 of the OWL composite sequ ence database, readily distinguishing them from all other integral mem brane proteins. With a 3-fold increase in the size of OWL, the fingerp rint has been updated and now finds 332 receptors that match ah the mo ths. The situation, however, has grown in complexity: 61 sequences mak e imperfect matches with the fingerprint, yielding a total of 393 'hit s'. The bulk of the partial hits are olfactory receptors: these appear to fall into discrete subfamilies in which one or more of the transme mbrane moths are either poorly matched or are not matched at all. Thes e results are supported by preliminary phylogenetic analyses, which sh ow the olfactory and various other partial matches clustering away fro m the main body of true hits. The approach has provided a powerful dia gnostic tool for identifying GPCRs, and results are consistent with pr evious observations that the pheromone, cAMP and secretin-like recepto rs belong to separate families-these bear their own unique sequence fi ngerprints by which they may be distinguished from the rhodopsin-like superfamily.