Structure of apolipoprotein A-I in spherical high density lipoproteins of different sizes
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- R. A. Gangani D. Silva
- *Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45237;
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- Rong Huang
- *Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45237;
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- Jamie Morris
- *Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45237;
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- Jianwen Fang
- Applied Bioinformatics Laboratory, University of Kansas, Lawrence, KS 66047;
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- Elena O. Gracheva
- Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158;
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- Gang Ren
- Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158;
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- Anatol Kontush
- Unité Mixte de Recherche S551, Institut National de la Santé et de la Recherche Médicale, Université Pierre et Marie Curie and Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpétrière, F-75013 Paris, France;
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- W. Gray Jerome
- Department of Pathology, Vanderbilt University Medical Center, Nashville, TN 37232;
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- Kerry-Anne Rye
- Lipid Research Group, Heart Research Institute, Camperdown NSW 2050, Australia,
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- W. Sean Davidson
- *Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45237;
書誌事項
- 公開日
- 2008-08-26
- DOI
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- 10.1073/pnas.0803626105
- 公開者
- Proceedings of the National Academy of Sciences
この論文をさがす
説明
<jats:p> Spherical high density lipoproteins (HDL) <jats:sup>†</jats:sup> predominate in human plasma. However, little information exists on the structure of the most common HDL protein, apolipoprotein (apo) A-I, in spheres vs. better studied discoidal forms. We produced spherical HDL by incubating reconstituted discoidal HDL with physiological plasma-remodeling enzymes and compared apoA-I structure in discs and spheres of comparable diameter (79–80 and 93–96 Å). Using cross-linking chemistry and mass spectrometry, we determined that the general structural organization of apoA-I was overall similar between discs and spheres, regardless of diameter. This was the case despite the fact that the 93 Å spheres contained three molecules of apoA-I per particle compared with only two in the discs. Thus, apoA-I adopts a consistent general structural framework in HDL particles—irrespective of shape, size and the number of apoA-Is present. Furthermore, a similar cross-linking pattern was demonstrated in HDL particles isolated from human serum. We propose the first experiment-based molecular model of apoA-I in spherical HDL particles. This model provides a new foundation for understanding how apoA-I structure modulates HDL function and metabolism. </jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 105 (34), 12176-12181, 2008-08-26
Proceedings of the National Academy of Sciences