Apolipoprotein E*dipalmitoylphosphatidylcholine particles are ellipsoidal in solution.
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 alpha-helical hairpin.
Peters-Libeu
Clare A
CA
Gladstone Institute of Neurological Disease, Biomolecular Resource Center Mass Spectrometry Facility, Department of Cell and Tissue Biology, University of California, San Francisco, CA 94158, USA.
Newhouse
Yvonne
Y
Hall
Steven C
SC
Witkowska
H Ewa
HE
Weisgraber
Karl H
KH
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry* / Q000302:isolation & purification; D000595:Amino Acid Sequence; D001057:Apolipoproteins E / Q000737:chemistry* / Q000302:isolation & purification; D018360:Crystallography, X-Ray; D006801:Humans; D013058:Mass Spectrometry; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D012996:Solutions; D013057:Spectrum Analysis
D001057:Apolipoproteins E; D012996:Solutions; D015060:1,2-Dipalmitoylphosphatidylcholine