Conformational changes of neuromedin B and delta sleep-inducing peptide induced by their interaction with lipid membranes as revealed by spectroscopic techniques and molecular dynamics simulation.
Static and dynamic spectroscopic properties of the tryptophanil emission in conjunction with circular dichroism (CD) spectroscopy and molecular dynamics are used to investigate the interactions of the neuropeptide neuromedin B (NMB) and the membrane-permeable delta sleep-inducing peptide (DSIP) with the membrane lipid phase. Our data indicate that in solution both peptides exist in energetically equivalent conformations, whereas in the presence of the membrane specific conformational states are stabilized. By changing from the aqueous to the lipid phase, the static and the dynamic fluorescence properties of the NMB's tryptophan residue are clearly affected: the fluorescence steady-state spectrum as well as the resolved fluorescence decay-associated spectra (DAS) are shifted to the blue with a significant increase of the fluorescence intensity of the second lifetime component (tau 2-DAS). On the other hand, in the lipid environment the same parameters of DSIP are negligibly affected as compared to the aqueous buffer. The CD and molecular dynamics analyses are consistent with these results and indicate that, while NMB assumes a helix-like conformation with the tryptophan residue in the apolar surface, DSIP adopts a globule-like structure with the indole ring that is surface-exposed. As previously found for neuromedin C (Polverini, E., Neyroz, P., Fariselli, P., Casadio, R., and Masotti, L., Biochem. Biophys. Res. Commun. 214, 663-668, 1995), for NMB the stabilized "lipophilic" structure also may favor the correct peptide-receptor contact and recognition. For DSIP, the lipid-stabilized conformation does not support an amphiphilic structure-driven peptide-membrane interaction and suggests a hydrophobicity-driven diffusion across the bilayer.
Polverini
E
E
Department of Biology, University of Bologna, Italy.
Casadio
R
R
Neyroz
P
P
Masotti
L
L
D002942:Circular Dichroism; D003701:Delta Sleep-Inducing Peptide / Q000737:chemistry*; D004134:Dimyristoylphosphatidylcholine; D005454:Fluorescence Polarization; D008051:Lipid Bilayers; D008244:Lysophosphatidylcholines; D008956:Models, Chemical; D008958:Models, Molecular; D015287:Neurokinin B / Q000031:analogs & derivatives* / Q000737:chemistry; D010718:Phosphatidylserines; D011487:Protein Conformation; D013050:Spectrometry, Fluorescence / Q000379:methods
D008051:Lipid Bilayers; D008244:Lysophosphatidylcholines; D010718:Phosphatidylserines; D003701:Delta Sleep-Inducing Peptide; D015287:Neurokinin B; C038393:neuromedin B; D004134:Dimyristoylphosphatidylcholine