Molecular dynamics of 1-palmitoyl-2-oleoylphosphatidylcholine membranes containing transmembrane alpha-helical peptides with alternating leucine and alanine residues.
The effects of the transmembrane alpha-helical peptide Ac-K(2)(LA)(12)K(2)-amide [(LA)(12)] on the molecular organization and dynamics of 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) membranes were investigated using conventional and saturation-recovery EPR observations of phosphatidylcholine spin labels, and the results were compared with our earlier, similar study of Ac-K(2)L(24)K(2)-amide (L(24)) [Subczynski, W. K., Lewis, R. N. A. H., McElhaney, R. N., Hodges, R. S., Hyde, J. S., and Kusumi, A. (1998) Biochemistry 37, 3156-3164]. At peptide-to-POPC ratios between 1/10 and 1/40, both methods (covering a time scale of 100 ps-10 micros) detect the presence of a single homogeneous membrane environment for both peptides, suggesting that these peptides are both well dispersed and that POPC is exchanging rapidly between the boundary and the bulk domains. The local diffusion-solubility product of oxygen molecules (oxygen transport parameter) in the membrane, studied by saturation-recovery EPR, decreases by a factor of about 2 by including 10 mol % (LA)(12) whereas incorporating L(24) has practically no effect. (LA)(12) increases the alkyl chain order of POPC more than L(24). L(24) increases hydrophobicity (decreases the degree of water penetration into the hydrophobic region of the membrane) more than does (LA)(12). We ascribe the much stronger effects of (LA)(12) on membrane order and dynamics to the increased roughness of its hydrophobic surface and also to the increased motional freedom of its leucine side chains. In L(24), the leucine side chains are packed tightly, giving a smooth hydrophobic surface. In (LA)(12), they are separated by the small methyl groups of the alanine side chains, giving them additional motional freedom and the ability to protrude between the phospholipid hydrocarbon chains. The frequency of gauche-trans isomerization of hydrocarbon chains and concentration of vacant pockets (voids) in the lipid bilayer are thus reduced, which decreases oxygen transport. This explanation was confirmed by calculating the orientational order of leucine side chains in (LA)(12) and L(24) from molecular dynamics simulation studies.
Subczynski
Witold K
WK
Biophysics Research Institute, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. subczyn@mcw.edu
Pasenkiewicz-Gierula
Marta
M
McElhaney
Ronald N
RN
Hyde
James S
JS
Kusumi
Akihiro
A
D000409:Alanine / Q000737:chemistry*; D001665:Binding Sites; D001692:Biological Transport; D004578:Electron Spin Resonance Spectroscopy; D007930:Leucine / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry; D008567:Membranes, Artificial; D008956:Models, Chemical; D008968:Molecular Conformation; D010100:Oxygen / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013696:Temperature
D008051:Lipid Bilayers; D008567:Membranes, Artificial; D010446:Peptide Fragments; D010713:Phosphatidylcholines; D007930:Leucine; D000409:Alanine; D010100:Oxygen; C028694:1-palmitoyl-2-oleoylphosphatidylcholine