THE OCTAPEPTIDE ANGIOTENSIN-II ADOPTS A WELL-DEFINED STRUCTURE IN A PHOSPHOLIPID ENVIRONMENT

The conformational properties adopted by angiotensin II in a phospholi pid micelle solution were studied by NMR spectroscopy and molecular mo delling. The octapeptide was found to assume a well-defined hairpin st ructure with its C- and N-termini approaching to within 0.76 nm of eac h other. Three of the residues had fixed side chain configurations: Ty r4 (g+), His6 (g-) and Val3 (g-). Consequently, the His6 and Tyr4 arom atic rings were consistently close together. Conformers containing a c is His6-Pro7 peptide bond were observed for the peptide in a purely aq ueous sample but completely disappeared when lipid vesicles were added to the sample. This result is explained by the existence of a very st able hydrogen bond between the Phe8 NH and the His6 carbonyl group of the lipid-solvated trans isomer, resulting in the formation of an inve rse gamma turn centered on Pro7, H-1-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-dimyris toyl-sn-glycero-3-phosphocholine bilayer vesicles. The data obtained w ere consistent with the structure derived for micelle-bound angiotensi n II, indicating that conformations adopted by the peptide hormone in the presence of micelles and lipid-bilayer vesicles are similar.