Molecular Biology of 5-HT Receptors

Within the past six months, isolation of cDNA or genomic clones has been reported for three 5-HT receptors, the 5-HT1C, 5-HT1A and 5-HT2 subtypes. As members of the G protein receptor superfamily, all three 5-HT receptor clones encode single-subunit proteins containing approximately 450 amino acids arrayed as seven interconnected transmembrane segments. Comparisons of 5-HT receptor sequence data with data from other G protein receptors provide suggestions for which amino acids may be involved in the binding of 5-HT and 5-HT antagonists to these receptors, and for certain key amino acids which may help confer 5-HT properties on these receptors. These rapid advances in our molecular understanding of 5-HT receptors also have significant implications for the ongoing debate over 5-HT receptor classification. In this article, Paul Hartig assembles the available molecular data and proposes a speculative model for the structure of G protein-coupled 5-HT receptors.