Peptide binding to lipid membranes. Spectroscopic studies on the insertion of a cyclic somatostatin analog into phospholipid bilayers.
The cyclic peptide SMS 201-995 (+)D-Phe1-Cys2-Phe3-D-Trp4-(+)Lys5-Thr6-++ +Cys7-Thr(ol)8 is an analog of somatostatin and binds to lipid membranes by an electrostatic/hydrophobic mechanism. The structural changes accompanying the binding process were investigated with circular dichroism (CD), fluorescence spectroscopy, and phosphorus and deuterium nuclear magnetic resonance. The peptide penetrates into the lipid bilayer and the binding is accompanied by a small change in the CD spectrum suggesting the formation of beta-ordered structures. The fluorescence emission spectrum of the tryptophan side chain exhibits a blue shift and an intensity enhancement of the emission maximum, providing evidence that this residue is located in the inner part of the phospholipid headgroup region with a dielectric constant of epsilon approximately 7. The peptide diffuses rapidly in the plane of the membrane, changing the lipid headgroup conformation. This was demonstrated by selectively deuterating the two choline segments and measuring the deuterium spectra as a function of the bound peptide concentrations. A linear variation of the quadrupole splitting with the mol fraction of bound peptide was observed. The molecular origin of this effect is a distinct change in the orientation of the phosphocholine dipole, moving the N+ end of the dipole away from the membrane surface into the water phase. This type of headgroup rotation appears to be the general response of the zwitterionic phosphocholine headgroup to cationic surface charges. However, peptides appear to be the most efficient modulators of the lipid headgroup structure known to date.
Beschiaschvili
G
G
Department of Biophysical Chemistry, Biocenter of the University of Basel, Switzerland.
Seelig
J
J
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D015282:Octreotide / Q000737:chemistry / Q000378:metabolism*; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D013050:Spectrometry, Fluorescence
D008051:Lipid Bilayers; D010743:Phospholipids; D015282:Octreotide