title: A single residue determines the distinct pharmacology of rat and human natriuretic peptide receptor-C.
abstract: 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.
authors.affiliation: Department of Cardiovascular Research, Genentech, Inc., South San Francisco, California 94080.
authors.forename: A M
authors.initials: AM
authors.lastname: Engel
authors.forename: J R
authors.initials: JR
authors.lastname: Schoenfeld
authors.forename: D G
authors.initials: DG
authors.lastname: Lowe
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D001483:Base Sequence; D002417:Cattle; D003001:Cloning, Molecular; D017931:DNA Primers / Q000737:chemistry; D006162:Guanylate Cyclase / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D051381:Rats; D017461:Receptors, Atrial Natriuretic Factor / Q000737:chemistry* / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
chemical_list: D017931:DNA Primers; D011993:Recombinant Fusion Proteins; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C