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Papers In Press, published online ahead of print May 1, 2007
J. Lipid Res., doi:10.1194/jlr.M600545-JLR200

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Journal of Lipid Research, Vol. 48, 1035-1044, May 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

Apolipoprotein E•dipalmitoylphosphatidylcholine particles are ellipsoidal in solution

Clare A. Peters-Libeu^*, Yvonne Newhouse^*, Steven C. Hall^,, H. Ewa Witkowska^, and Karl H. Weisgraber^1,*,**,

^* Gladstone Institute of Neurological Disease, University of California, San Francisco, CA 94158
Biomolecular Resource Center Mass Spectrometry Facility, University of California, San Francisco, CA 94158
Department of Cell and Tissue Biology, University of California, San Francisco, CA 94158
^** Department of Pathology, University of California, San Francisco, CA 94158
Cardiovascular Research Institute, University of California, San Francisco, CA 94158

The online version of this article (available at http://www.jlr.org) contains supplementary data in the form of a table.

Published, JLR Papers in Press, February 17, 2007.

¹ To whom correspondence should be addressed. e-mail: kweisgraber{at}gladstone.ucsf.edu

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 -helical hairpin.

Supplementary key words lipoprotein • small-angle X-ray scattering • phospholipid • apolipoprotein A-I

Abbreviations: apo E, apolipoprotein E; DMPC, dimyristoylphosphatidylcholine; DPPC, dipalmitoylphosphatidylcholine; MS/MS, tandem mass spectrometry; ESI, electrospray ionization; POPC, 1-palmitoyl-2-oleoylphosphatidylcholine; SAXS, small-angle X-ray scattering

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