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Identification of a novel dual angiotensin II/vasopressin receptor on the basis of molecular recognition theory

Nature Medicine volume 1, pages 1074–1081 (1995)Cite this article

Abstract

The molecular recognition theory suggests that binding sites of interacting proteins, for example, peptide hormone and its receptor binding site, were originally encoded by and evolved from complementary strands of genomic DNA. To test this theory, we screened a rat kidney complementary DNA library twice: first with the angiotensin II (All) followed by the vasopressin (AVP) antisense oligonucleotide probe, expecting to isolate cDNA clones of the respective receptors. Surprisingly, the identical cDNA clone was isolated twice independently. Structural analysis revealed a single receptor polypeptide with seven predicted transmembrane regions, distinct All and AVP putative binding domains, a Gs, protein–activation motif, and an internalization recognition sequence. Functional analysis revealed specific binding to both All and AVP as well as All– and AVP–induced coupling to the adenylate cyclase second messenger system. Site–directed mutagenesis of the predicted All binding domain obliterates All binding but preserves AVP binding. This corroborates the dual nature of the receptor and provides direct molecular genetic evidence for the molecular recognition theory.

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Authors and Affiliations

  1. Section of Molecular Genetics, Whitaker Cardiovascular Institute, Boston University School of Medicine, 80 East Concord Street, Boston, Massachusetts, 02118, USA

    Nelson Ruiz-Opazo, Kaoru Akimoto & Victoria L.M. Herrera

  2. Section of Cardiology, Whitaker Cardiovascular Institute, Boston University School of Medicine, 80 East Concord Street, Boston, Massachusetts, 02118, USA

    Victoria L.M. Herrera

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  1. Nelson Ruiz-Opazo
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Ruiz-Opazo, N., Akimoto, K. & Herrera, V. Identification of a novel dual angiotensin II/vasopressin receptor on the basis of molecular recognition theory. Nat Med 1, 1074–1081 (1995). https://doi.org/10.1038/nm1095-1074

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