Conformational changes of phospholipid headgroups induced by a cationic integral membrane peptide as seen by deuterium magnetic resonance

Abstract

Deuterium nuclear magnetic resonance (2H NMR) was used to study the interaction of a cationic amphiphilic peptide with pure DMPC membranes and with mixed bilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylserine (DMPS). The choline and serine headgroups were selectively deuteriated at the alpha and beta positions. The amphiphilic peptide, with 20 leucine residues in the hydrophobic core and two cationic hydrophilic lysine residues at each end, spanned the lipid bilayer. Although 2H NMR experiments using DMPC with perdeuteriated fatty acyl chains showed that the average order parameter of the hydrophobic region was not significantly modified by the incorporation of the amphiphilic peptide, for either DMPC or DMPC/DMPS (5:1) bilayers, large perturbations of the quadrupolar splittings of the choline and serine headgroups were observed. The results obtained with the DMPC headgroup suggest that the incorporation of the cationic peptide in both DMPC and DMPC/DMPS (5:1) bilayers leads to a structural perturbation directly related to the net charge on the membrane surface. The magnitude of the observed effect seems to be similar to those observed previously with other cationic molecules [Seelig, J., MacDonald, P.M., & Scherer, P.G. (1987) Biochemistry 26, 7535-7541]. Two of the three quadrupolar splittings of the PS headgroup exhibited large variations in the presence of the amphiphilic peptide, while the third one remained unchanged. Our data have led us to propose a model describing the influence of membrane surface charges on headgroup conformation. In this model, the surface charge is represented as a uniform charge distribution. The electric field due to the charges produces a torque which rotates the polar headgroups.(ABSTRACT TRUNCATED AT 250 WORDS)

Different Membrane Anchoring Positions of Tryptophan and Lysine in Synthetic Transmembrane α-Helical Peptides

“…KALP23 has only a small effect on acyl chain order and dynamics, in agreement with work on a comparable Lysflanked polyleucine peptide (38,39). Nevertheless, earlier studies have shown that Lys-flanked polyleucine peptides are capable of inducing systematic acyl chain ordering and disordering (40,41).…”

Conformational response of the phosphatidylcholine headgroup to bilayer surface charge: torsion angle constraints from dipolar and quadrupolar couplings in bicelles

“…Figure 11 shows that, relative to the neutral case, cationic surface charge causes the P-N vector to tilt upward, whereas anionic surface charge causes the P-N vector to tilt downwards toward the bicelle surface. This is in accord with the earliest models of the phosphocholine response to surface charges 7,18 and with the analysis of the case of cationic surface charge by Akutsu and Nagamori. 21 Figure 12(A) shows that the average P-N tilt changes in a continuous fashion with increasing cationic or anionic surface charge, but that cationic charge produces a far greater absolute effect.…”

“…7,18 Interestingly, they predicted changes in the 13 C˛-31 P dipolar coupling for cationic versus neutral versus anionic surface charge that are confirmed here experimentally for the first time. Nevertheless, these authors concluded that observed quadrupolar splittings could only be reproduced if the phosphocholine group underwent internal torsion angle changes, rather than reorienting as a unit as postulated in the choline tilt model.…”

“…16 Scherer and Seelig 17 proposed that electrostatic charge at bilayer surfaces produces a change in the angle of tilt of the P-N vector of the phosphocholine group about a hinge corresponding to the glycerol C 3 -O-P dihedral angle. Subsequently, a model was developed by Roux et al 7 in which the P-N dipole was driven to reorient in the electrostatic field emanating outwards from the bilayer surface in the presence of surface charge. The result was a tilting of the P-N dipole towards a more perpendicular orientation in the presence of cationic surface charge and towards a more parallel orientation in the presence of anionic surface charge.…”

Weak interaction of spectrin with phosphatidylcholine‐phosphatidylserine multilayers: A 2H and 31P NMR study

“…This result can be compared with other deuterium NMR studies of the interaction between PS and various proteins [20][21][22]301, which show that positively charged proteins which do not penetrate within the bilayer have detectable (though weak) effects on the conformation of PS head group [20,21]. Proteins which are both charged and able to penetrate into the membrane surface have a much larger effect on the conformation of PS head group [30]. The absence of any effect of spectrin on the conformation of PS head group suggests that the interaction of spectrin with these lipids is purely superficial and has no hydrophobic component, despite the presence of some hydrophobic segments on the protein [31].…”