We report the cloning and expressing of rat natriuretic peptide receptor-C (NPR-C), which binds naturally occurring and synthetic ligands with higher affinity than human NPR-C. Using rat/human hybrids and site-directed mutagenesis, we identified residue 188, Ala for rat and Ile for human, which modulates hormone binding. Orthologous mutagenesis at position 188 for either rNPR-C or hNPR-C results in a complete reversal of the pharmacology. To our knowledge, this is the first example of a single transmembrane domain receptor for which a single residue dictates the ligand binding properties; previous examples are limited to seven transmembrane receptors.
Gene Ontology Annotations
