Lipid headgroup superlattice modulates the activity of surface-acting cholesterol oxidase in ternary phospholipid/cholesterol bilayers.
The relationship between the molecular organization of lipid headgroups and the activity of surface-acting enzyme was examined using a bacterial cholesterol oxidase (COD) as a model. The initial rate of cholesterol oxidation by COD in fluid state 1-palmitoyl-2-oleoyl-phosphatidylethanolamine/1-palmitoyl-2-oleoyl-phosphatidylcholine/cholesterol (POPE/POPC/CHOL) bilayers was measured as a function of POPE-to-phospholipid mole ratio (X(PE)) and cholesterol-to-lipid mole ratio (X(CHOL)) at 37 degrees C. At X(PE) = 0, the COD activity changed abruptly at X(CHOL) approximately 0.40, whereas major activity peaks were detected at X(PE) approximately 0.18, 0.32, 0.50, 0.64, and 0.73 when X(CHOL) was fixed to 0.33 or 0.40. At a fixed X(CHOL) of 0.50, the COD activity increased progressively with PE content and exhibited small peaks or kinks at X(PE) approximately 0.40, 0.50, 0.58, 0.69, and 0.81. When X(PE) and X(CHOL) were systematically varied within a narrow 2-D lipid composition window, an onset of COD activity at X(CHOL) approximately 0.40 and the elimination of the activity peak at X(PE) approximately 0.64 for X(CHOL) >0.40 were clearly observed. Except for X(PE) approximately 0.40 and 0.58, the observed critical PE mole ratios agree closely (+/-0.03) with those predicted by a headgroup superlattice model (Virtanen, J.A., et al. (1998) Proc. Natl. Acad. Sci. U.S.A. 95, 4964-4969; Cannon, B., et al. (2006) J. Phys. Chem. B 110, 6339-6350), which proposes that lipids with headgroups of different sizes tend to adopt regular, superlattice-like distributions at discrete and predictable compositions in fluid lipid bilayers. Our results indicate that headgroup superlattice domains exist in lipid bilayers and that they may play a crucial role in modulating the activity of enzymes acting on the cell membrane surface.
Cheng
Kwan Hon
KH
Department of Physics, Texas Tech University, Lubbock, Texas 79409, USA. vckhc@ttacs.ttu.edu
Cannon
Brian
B
Metze
Jennifer
J
Lewis
Anthony
A
Huang
Juyang
J
Vaughn
Mark W
MW
Zhu
Qing
Q
Somerharju
Pentti
P
Virtanen
Jorma
J
D002784:Cholesterol / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D002789:Cholesterol Oxidase / Q000737:chemistry / Q000378:metabolism*; D003198:Computer Simulation; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D008962:Models, Theoretical; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*
D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010743:Phospholipids; C057561:1-palmitoyl-2-oleoylphosphatidylethanolamine; D002784:Cholesterol; D002789:Cholesterol Oxidase; C028694:1-palmitoyl-2-oleoylphosphatidylcholine