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Chapter 9,604

The octapeptide angiotensin II adopts a well-defined structure in a phospholipid environment

Carpenter, K.A.; Wilkes, B.C.; Schiller, P.W.

European Journal of Biochemistry 251(1-2): 448-453

1998


ISSN/ISBN: 0014-2956
PMID: 9492317
DOI: 10.1046/j.1432-1327.1998.2510448.x
Accession: 009603619

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The conformational properties adopted by angiotensin II in a phospholipid micelle solution were studied by NMR spectroscopy and molecular modelling. The octapeptide was found to assume a well-defined hairpin structure with its C- and N-termini approaching to within 0.76 nm of each other. Three of the residues had fixed side chain configurations; Tyr4 (g+), His6 (g-) and Val3 (g-). Consequently, the His6 and Tyr4 aromatic rings were consistently close together. Conformers containing a cis His6-Pro7 peptide bond were observed for the peptide in a purely aqueous sample but completely disappeared when lipid vesicles were added to the sample. This result is explained by the existence of a very stable hydrogen bond between the Phe8 NH and the His6 carbonyl group of the lipid-solvated trans isomer, resulting in the formation of an inverse gamma turn centered on Pro7. 1H-NMR selective line broadening was apparent for several of the angiotensin II protons upon titration of an aqueous sample with less than stoichiometric amounts of 1,2-dimyristoyl-sn-glycero-3-phosphocholine bilayer vesicles. The data obtained were consistent with the structure derived for micelle-bound angiotensin II, indicating that conformations adopted by the peptide hormone in the presence of micelles and lipid-bilayer vesicles are similar.

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