Apolipoprotein E•dipalmitoylphosphatidylcholine particles are ellipsoidal in solutions⃞
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 neurodegenerat...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2007-05-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520435497 |
| _version_ | 1818676147866566656 |
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| author | Clare A. Peters-Libeu Yvonne Newhouse Steven C. Hall H. Ewa Witkowska Karl H. Weisgraber |
| author_facet | Clare A. Peters-Libeu Yvonne Newhouse Steven C. Hall H. Ewa Witkowska Karl H. Weisgraber |
| author_sort | Clare A. Peters-Libeu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-17T08:38:52Z |
| format | Article |
| id | doaj.art-6b5f941573e24c49b3341a2386771699 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T08:38:52Z |
| publishDate | 2007-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-6b5f941573e24c49b3341a23867716992022-12-21T21:56:25ZengElsevierJournal of Lipid Research0022-22752007-05-0148510351044Apolipoprotein E•dipalmitoylphosphatidylcholine particles are ellipsoidal in solutions⃞Clare A. Peters-Libeu0Yvonne Newhouse1Steven C. Hall2H. Ewa Witkowska3Karl H. Weisgraber4Gladstone Institute of Neurological Disease, University of California, San Francisco, CA 94158Gladstone Institute of Neurological Disease, University of California, San Francisco, CA 94158Biomolecular Resource Center Mass Spectrometry Facility, University of California, San Francisco, CA 94158; Department of Cell and Tissue Biology, University of California, San Francisco, CA 94158Biomolecular Resource Center Mass Spectrometry Facility, University of California, San Francisco, CA 94158; Department of Cell and Tissue Biology, University of California, San Francisco, CA 94158Gladstone Institute of Neurological Disease, 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 94158Apolipoprotein 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.http://www.sciencedirect.com/science/article/pii/S0022227520435497lipoproteinsmall-angle X-ray scatteringphospholipidapolipoprotein A-I |
| spellingShingle | Clare A. Peters-Libeu Yvonne Newhouse Steven C. Hall H. Ewa Witkowska Karl H. Weisgraber Apolipoprotein E•dipalmitoylphosphatidylcholine particles are ellipsoidal in solutions⃞ Journal of Lipid Research lipoprotein small-angle X-ray scattering phospholipid apolipoprotein A-I |
| title | Apolipoprotein E•dipalmitoylphosphatidylcholine particles are ellipsoidal in solutions⃞ |
| title_full | Apolipoprotein E•dipalmitoylphosphatidylcholine particles are ellipsoidal in solutions⃞ |
| title_fullStr | Apolipoprotein E•dipalmitoylphosphatidylcholine particles are ellipsoidal in solutions⃞ |
| title_full_unstemmed | Apolipoprotein E•dipalmitoylphosphatidylcholine particles are ellipsoidal in solutions⃞ |
| title_short | Apolipoprotein E•dipalmitoylphosphatidylcholine particles are ellipsoidal in solutions⃞ |
| title_sort | apolipoprotein e•dipalmitoylphosphatidylcholine particles are ellipsoidal in solutions⃞ |
| topic | lipoprotein small-angle X-ray scattering phospholipid apolipoprotein A-I |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520435497 |
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