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Interaction of angiotensin II with the C‐terminal 300–320 fragment of the rat angiotensin II receptor AT 1a monitored by NMR
Author(s) -
D'Amelio Nicola,
Gaggelli Elena,
Gaggelli Nicola,
Lozzi Luisa,
Neri Paolo,
Valensin Daniela,
Valensin Gianni
Publication year - 2003
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.10426
Subject(s) - chemistry , angiotensin ii , intermolecular force , crystallography , peptide , stereochemistry , stacking , molecular dynamics , two dimensional nuclear magnetic resonance spectroscopy , proton nmr , angiotensin receptor , receptor , molecule , computational chemistry , biochemistry , organic chemistry
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