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标题：Structure of apolipoprotein B-100 in low density lipoproteins
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作者：Jere P. Segrest ; Martin K. Jones ; Hans De Loof 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2001
卷号：42
期号：9
页码：1346-1367
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：There is general consensus that amphipathic α-helices and β sheets represent the major lipid-associating motifs of apolipoprotein (apo)B-100. In this review, we examine the existing experimental and computational evidence for the pentapartite domain structure of apoB. In the pentapartite nomenclature presented in this review (NH₂-βα ₁-β₁-α₂-β₂-α₃-COOH), the original α₁ globular domain (Segrest, J. P. et al. 1994. Arterioscler. Thromb. 14: 1674–1685) is expanded to include residues 1–1,000 and renamed the βα ₁ domain. This change reflects the likelihood that the βα ₁ domain, like lamprey lipovitellin, is a globular composite of α-helical and β-sheet secondary structures that participates in lipid accumulation in the co-translationally assembled prenascent triglyceride-rich lipoprotein particles. Evidence is presented that the hydrophobic faces of the amphipathic β sheets of the β₁ and β₂ domains of apoB-100 are in direct contact with the neutral lipid core of apoB-containing lipoproteins and play a role in core lipid organization. Evidence is also presented that these β sheets largely determine LDL particle diameter. Analysis of published data shows that with a reduction in particle size, there is an increase in the number of amphipathic helices of the α₂ and α₃ domains associated with the surface lipids of the LDL particle; these increases modulate the surface pressure decreases caused by a reduction in radius of curvature. The properties of the LDL receptor-binding region within the overall domain structure of apoB-100 are also discussed. Finally, recent three-dimensional models of LDL obtained by cryoelectron microscopy and X-ray crystallography are discussed. These models show three common features: a semidiscoidal shape, a surface knob with the dimensions of the βC globular domain of lipovitellin, and planar multilayers in the lipid core that are approximately 35 Å apart; the multilayers are thought to represent cholesteryl ester in the smectic phase. These models present a conundrum: are LDL particles circulating at 37°C spheroidal in shape, as generally assumed, or are they semidiscoidal in shape, as suggested by the models? The limited evidence available supports a spheroidal shape. —Segrest, J. P., M. K. Jones, H. De Loof, and N. Dashti. Structure of apolipoprotein B-100 in low density lipoproteins. J. Lipid Res. 2001. 42: 1346–1367.
关键词：amphipathic β sheets ; amphipathic α-helices ; cryoelectron microscopy ; X-ray crystallography ; boundary lipid ; smectic phase ; lipid phase transition ; LDL receptor-binding domain