H-2 NMR-STUDIES OF A MYRISTOYLATED PEPTIDE IN NEUTRAL AND ACIDIC PHOSPHOLIPID BICELLES

Deuterium NMR spectra of Myr-d(27)-GNAAAAKKGSEQES (Cat14), the N-termi nal 14-residue peptide from the catalytic subunit of cAMP-dependent pr otein kinase A (PKA), illustrate how magnetically aligned neutral and acidic phospholipid bicelles can be used to characterize the ordering and mode of binding of peptides to membranes. Since Cat14 is electrica lly neutral, the major interaction responsible for binding is the inse rtion of the myristoyl group into the hydrophobic core of the bilayer. The inclusion of 25% phosphatidylserine or phosphatidylglycerol into phosphatidylcholine bicelles results in a moderate increase in the ord ering of the peptide relative to the bicelle normal, presumably becaus e of favorable electrostatic interactions between the phospholipid hea dgroups and the two lysines in positions 7 and 8. Successful preparati on of acidic bicelles was achieved by careful adjustment of lipid comp osition, pH and ionic strength.