Melanotropic peptides-lipid bilayer interaction. Comparison of the hormone alpha-MSH to a biologically more potent analog.
The interaction of the native peptide alpha-melanocyte stimulating hormone (alpha-MSH) and the biologically more active analog [Nle4, D-Phe7]-alpha-MSH(MSH-I) with lipid vesicles was studied by spin label electron spin resonance (ESR) spectroscopy and circular dichroism (CD). Using spin labels located at the membrane interface and at different depths along the acyl chain, it was shown that the binding of both peptides to the membrane induces tighter lipid packing at all the monitored positions. However, the effect of the analog on the spin label ESR parameters was much more evident, and suggested that it penetrates farthest into the lipid matrix than the native molecule. Lipid partition coefficients were calculated based on the effect the peptides cause on the ESR spectra of spin labels incorporated in the membrane. For the biologically more potent peptide, the partition coefficient was found to be about 4-times greater than that of the native hormone. For the same concentration of peptide bound to the membrane, MSH-I was found to cause a slightly greater effect on the membrane structure than alpha-MSH, in accord with its possible deeper penetration into the bilayer. CD spectra in aqueous solution and in the alpha-helix inducing solvent 2,2,2-trifluoroethanol showed that the two peptides have somewhat different structures in solution, though similar conformational changes occur in both peptides as a result of their interaction with negatively charged vesicles or micelles. The higher peptide-lipid association constant and the deeper penetration of the analog into lipid bilayers could be related to its greater activity and/or prolonged action.
Biaggi
M H
MH
Instituto de Física, Universidade de São Paulo, Brazil.
Riske
K A
KA
Lamy-Freund
M T
MT
D000345:Affinity Labels / Q000737:chemistry / Q000378:metabolism; D002942:Circular Dichroism; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D010715:Phosphatidylglycerols / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D000521:alpha-MSH / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*
D000345:Affinity Labels; D008051:Lipid Bilayers; D010715:Phosphatidylglycerols; D000521:alpha-MSH; C027756:MSH, 4-Nle-7-Phe-alpha-; C002773:dimyristoylphosphatidylglycerol; D004134:Dimyristoylphosphatidylcholine