Apolipoprotein E•dipalmitoylphosphatidylcholine particles are ellipsoidal in solutions⃞

• Main Authors: Clare A. Peters-Libeu, Yvonne Newhouse, Steven C. Hall, H. Ewa Witkowska, Karl H. Weisgraber
• Format: Article
• Language: English
• Published: Elsevier 2007-05-01
• Series: Journal of Lipid Research
• Subjects: lipoprotein; small-angle X-ray scattering; phospholipid; apolipoprotein A-I
• Online Access: http://www.sciencedirect.com/science/article/pii/S0022227520435497

Apolipoprotein E (apoE) is a major protein component of cholesterol-transporting lipoprotein particles in the central nervous system and in plasma. Polymorphisms of apoE are associated with cardiovascular disease and with a predisposition to Alzheimer's disease and other forms of neurodegeneration. For full biological activity, apoE must be bound to a lipoprotein particle. Complexes of apoE and phospholipid mimic many of these activities. In contrast to a widely accepted discoidal model of apoA-I bound to dimyristoylphosphatidylcholine, which is based on solution studies, an X-ray diffraction study of apoE bound to dipalmitoylphosphatidylcholine (DPPC) indicated that apoE•DPPC particles are quasi-spheroidal and that the packing of the phospholipid core is similar to a micelle. Using small-angle X-ray scattering, we show that apoE•DPPC particles in solution are ellipsoidal and that the shape of the phospholipid core is compatible with a twisted-bilayer model. The proposed model is consistent with the results of mass spectrometric analysis of products of limited proteolysis. These revealed that the nonlipid-bound regions of apoE in the particle are consistent with an α-helical hairpin.