A molecular view on the interaction of the trojan peptide penetratin with the polar interface of lipid bilayers.
Penetratin belongs to the family of Trojan peptides that effectively enter cells and therefore can be used as cargoes for agents that are unable to penetrate the cell membrane. We applied polarized infrared spectroscopy in combination with the attenuated total reflection technique to extract information before penetratin binding to lipid membranes with molecular resolution. The amide I band of penetratin in the presence of zwitterionic dimyristoylphosphatidylcholine and of anionic lipid membranes composed of dioleoylphosphatidylcholine and dioleoylphosphatidylglycerol shows the characteristics of an antiparallel beta-sheet with a small fraction of turns. Both signatures have been interpreted in terms of a hairpin conformation. The infrared linear dichroism of the amide I band indicates that the peptide chain orients in an oblique fashion whereas the plane of the sheet aligns virtually parallel with respect to the membrane surface. The weak effect of the peptide on dimyristoylphosphatidylcholine gives indication of its superficial binding where the charged lysine and arginine side chains form H-bonds to the phosphate oxygens of the surrounding lipids. The determinants for internalization of penetratin appear to be a peptide sequence with a distribution of positively charged residues along a beta-sheet conformation, which enables the anchoring of the peptide in the polar part of the membranes and the effective compensation of anionic lipid charges.
Binder
Hans
H
Department of Biophysical Chemistry, Umeå University, Umea, Sweden. binder@rz.uni-leipzig.de
Lindblom
Göran
G
D001120:Arginine / Q000737:chemistry; D002352:Carrier Proteins / Q000737:chemistry*; D057846:Cell-Penetrating Peptides; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D008239:Lysine / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared
D002352:Carrier Proteins; D057846:Cell-Penetrating Peptides; D008051:Lipid Bilayers; D010455:Peptides; D001120:Arginine; C414409:penetratin; D008239:Lysine; D004134:Dimyristoylphosphatidylcholine