Unexpected Binding of an Octapeptide to the Angiotensin II Receptor

• Published in: Proceedings of the National Academy of Sciences - PNAS 1987-12, Vol.84 (24), p.9219-9222
• Main Authors: Soffer, R. L., Bandyopadhyay, S., Rosenberg, E., Hoeprich, P., Teitelbaum, A., Brunck, T., Colby, C. B., Gloff, C.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino acids; Angiotensin II - immunology; Angiotensin II - metabolism; Angiotensin receptors; Animals; Binding, Competitive; Biochemistry; Biological and medical sciences; Cell physiology; Enzymes; Fundamental and applied biological sciences. Psychology; Hormonal regulation; Immunoglobulins; Inhibitory concentration 50; Medical sciences; Molecular and cellular biology; Oligopeptides - metabolism; Physiological regulation; Rabbits; Receptors; Receptors, Angiotensin - immunology; Receptors, Angiotensin - metabolism; Resins; Structure-Activity Relationship
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.84.24.9219

An octapeptide, TBI-22 (Lys-Gly-Val-Tyr-Ile-His-Ala-Leu), inhibited binding of angiotensin II by a solubilized angiotensin receptor partially purified from rabbit liver. This inhibition appears to result from competition for binding to the same receptor. Radioiodinated TBI-22, like angiotensin II, bound to the solubilized receptor with an affinity such that the binding was inhibited 50% by unlabeled TBI-22 or angiotensin II at nanomolar concentrations. The binding reaction, like that for angiotensin II, required p-chloromercuriphenylsulfonic acid and was reversed in the presence of dithiothreitol. TBI-22 and angiotensin II share the sequence Val-Tyr-Ile-His; this tetrapeptide alone, however, did not inhibit binding of angiotensin II. Replacement of the tyrosine residue by aspartic acid in TBI-22 greatly reduced the ability of the peptide to compete with angiotensin II for binding, suggesting an important contribution of this residue to the configuration required for recognition by the receptor.