Interaction of angiotensin II with the C-terminal 300–320 fragment of the rat angiotensin II receptor AT1a monitored by NMR

✍ Scribed by Nicola D'Amelio; Elena Gaggelli; Nicola Gaggelli; Luisa Lozzi; Paolo Neri; Daniela Valensin; Gianni Valensin

• Publisher: Wiley (John Wiley & Sons)
• Year: 2003
• Tongue: English
• Weight: 319 KB
• Volume: 70
• Category: Article
• ISSN: 0006-3525
• DOI: 10.1002/bip.10426

✦ Synopsis

Abstract

Interaction between angiotensin II (Ang II) and the fragment peptide 300–320 (fCT^300–320^) of the rat angiotensin II receptor AT~1a~ was demonstrated by relaxation measurements, NOE effects, chemical shift variations, and CD measurements. The correlation times modulating dipolar interactions for the bound and free forms of Ang II were estimated by the ratio of the nonselective and single‐selective longitudinal relaxation rates. The intermolecular NOEs observed in NOESY spectra between HN protons of ^9^Lys~fCT~ and ^6^His~ang~, ^10^Phe~fCT~ and ^8^Phe~ang~, HN proton of ^3^Tyr~fCT~ and Hα of ^4^Tyr~ang~, ^5^Phe~fCT~Hδ and Hα of ^4^Tyr~ang~ indicated that Ang II aromatic residues are directly involved in the interaction, as also verified by relaxation data. Some fCT^300–320^ backbone features were inferred by the CSI method and CD experiments revealing that the presence of Ang II enhances the existential probability of helical conformations in the fCT fragment. Restrained molecular dynamics using the simulated annealing protocol was performed with intermolecular NOEs as constraints, imposing an α‐helix backbone structure to fCT^300–320^ fragment. In the built model, one strongly preferred interaction was found that allows intermolecular stacking between aromatic rings and forces the peptide to wrap around the ^6^Leu side chain of the receptor fragment. © 2003 Wiley Periodicals, Inc. Biopolymers 70: 134–144, 2003