Study of bradykinin conformation in the presence of model membrane by Nuclear  Magnetic Resonance and molecular modelling.
The conformation of bradykinin (BK), Arg1-Pro2-Pro3-Gly4-Phe5-Ser6-Pro7-Phe8-Arg9, was investigated by Nuclear Magnetic Resonance (NMR) spectroscopy and Monte Carlo simulation in two different media, i.e. in pure aqueous solution and in the presence of phospholipid vesicles. Monolamellar liposomes are a good model for biological membranes and mimic the environment experienced by bradykinin when interacting with G-protein coupled receptors (GPCRs). The NMR spectra showed that lipid bilayers induced a secondary structure in the otherwise inherently flexible peptide. The results of ensemble calculations revealed conformational changes occurring rapidly on the NMR time scale and allowed for the identification of different families of conformations that were averaged to reproduce the NMR observables. These structural results supported the hypothesis of the central role played by the peptide C-terminal domain in biological environments, and provided an explanation for the different biological behaviours observed for bradykinin
Bonechi
Claudia
C
Department of Chemical and Biosystem Sciences and CSGI, University of Siena, Via A. Moro 2, 53100 Siena, Italy. cbonechi@unisi.it
Ristori
Sandra
S
Martini
Giacomo
G
Martini
Silvia
S
Rossi
Claudio
C
D001920:Bradykinin / Q000737:chemistry*; D003198:Computer Simulation; D008081:Liposomes / Q000737:chemistry; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011487:Protein Conformation
C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D008081:Liposomes; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C017251:1,2-oleoylphosphatidylcholine; D001920:Bradykinin