Search

The interaction of a 19 amino acid vesicular stomatitis virus G protein fragment (GTWLNPGFPPQSCGYATVT) with phosphatidylserine-containing model membranes was investigated using solution-phase 1d and 2d 1H NMR spectroscopy and intrinsic tryptophan fluorescence. Results of these studies show that this peptide interacts with model membranes containing negatively charged phospholipids. The interaction is modulated by both ionic and hydrophobic factors and appears to be dependent on the fluidity and lipid packing of the target bilayer. The data further suggest the existence of two isomeric forms of this peptide, which react differentially with model membranes. Upon binding, 2d 1H NOESY and tryptophan fluorescence data indicate penetration of the tryptophan residue into the bilayer. A model is proposed for the interaction of the peptide with model membranes, consistent with the experimental findings.

The natural chiral phospholipid substrates for the plasma membrane aminophospholipid translocator are L-alpha-phosphatidyl-L-serine and L-alpha-phosphatidylethanolamine. The glyceric D-stereoisomers of these lipids, D-alpha-phosphatidyl-L-serine and D-alpha-phosphatidylethanolamine, are not translocated (Martin, O.C. and Pagano, R.E. (1987) J. Biol. Chem. 262, 5890-5898). We have synthesized a diastereomer of phosphatidylserine, L-alpha-phosphatidyl-D-serine, to study the effects of headgroup stereochemistry on translocation. The diastereomer was synthesized as the dilauroyl (12:0) species, and the translocation was monitored by human erythrocyte morphology changes at 25 degrees C and 37 degrees C. Unlike other phosphatidylserine stereoisomers, L-alpha-phosphatidyl-D-serine is translocated to the same degree as the natural L,L-isomer. Incorporation of apparently equal amounts of the L,D- and L,L-diastereomers does produce minor quantitative differences in the cell morphological response, possibly as a result of differences in lipid packing of the two isomers.