Full activation of chimeric receptors by hybrids between parathyroid hormone and calcitonin - Evidence for a common pattern of ligand-receptor interaction

Calcitonin (CT) and parathyroid hormone (PTH), whose receptors belong to the same family of G protein-coupled receptors, share no amino acid sequence homology and selectively activate either CT or PTH receptors. We now show, however, that reciprocal hybrid ligands (CT/PTH and PTH/CT), which do not activate the ''wild-type'' receptors, activate PTH/CT and CT/PTH receptor chimeras, respectively, Our findings indicate that PTH and CT share a similar architecture with at least two functional, receptor-specific domains, These domains are sufficiently independent to permit synthetic hybrid ligands to efficiently activate appropriate receptor chimeras. Therefore, both ligands follow, despite their very different primary sequences, a common pattern of ligand-receptor interaction.