Role of Asp297 of the AT2 receptor in high-affinity binding to different peptide ligands

• Published in: Peptides (New York, N.Y. : 1980) Vol. 22; no. 12; pp. 2145 - 2149
• Main Authors: Knowle, Dieter, Kurfis, Jayson, Gavini, Narasaiah, Pulakat, Lakshmidevi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2001
• Subjects: Amino Acid Sequence; Angiotensin II; Aspartic Acid - metabolism; AT2 receptor; Ligands; Molecular Sequence Data; Phospholipase C; Protein Binding; Receptors, Angiotensin - chemistry; Receptors, Angiotensin - metabolism; Third extracellular loop; Transmembrane domain; Xenopus oocytes; Xenopus oocytes; Transmembrane domain; Third extracellular loop; Angiotensin II; AT2 receptor; Phospholipase C
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/S0196-9781(01)00553-8

To determine how ligand-receptor interaction is affected by the charges of the amino acids at position 2 of the ligands and position 297 of the AT2 receptor, we generated the Asp297Lys mutant of AT2 and a ligand SarAsp 2Ile. Asp297Lys mutant lost affinity to Ang II and SarIle however retained partial affinity to 125I-CGP42112A. The SarAsp 2Ile had high affinity to Asp297Lys (IC 503.5nM) and partial affinity to the AT2 (IC 5015nM). Therefore, not only the charge, but also the length of the side arms of the amino acids at position 2 of the ligand and position 297 of the receptor affect their interaction.