Conserved sequence motifs of olfactory receptor-like proteins may participate in upstream and downstream signal transduction

Olfactory receptor-like proteins (ORLs) are seven transmembrane domain G pr otein-coupled receptors. We hypothesize that, in contrast with the hypervar iable regions that may interact with a variety of odor ligands, the externa l and internal segments of the ORLs contain conserved regions that may inte ract with conserved olfactory binding proteins or direct axon guidance, and with G proteins, respectively. To test this hypothesis, a comprehensive an alysis using the multiple expectation maximization for motif elicitation di scovery tool was performed in all the full-length ORL clones deposited in t he public section of the olfactory receptor database. Ten motifs have been identified that are present in all the olfactory receptors, in the same ord er, and are not present in other G protein-coupled receptors. These motifs are concentrated either in the extracellular most or the intracellular-most parts of the receptors. The generality of these motifs was verified by the ir existence in the partial ORLs and 28 newly identified human receptors. T he existence and localization of these motifs, suggest that they may be inv olved in the interactions of the receptors with their upstream and downstre am signaling partners. In addition, the motifs present an additional to ove rall homology criterion for ORL family definition.