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Journal of Lipid Research, Vol. 42, 1346-1367, September 2001
Copyright © 2001 by Lipid Research, Inc.

Review Article

Structure of apolipoprotein B-100 in low density lipoproteins

Correspondence to: Jere P. Segrest, To whom correspondence should be addressed., segrest{at}uab.edu (E-mail)

There is general consensus that amphipathic -helices and ß 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-ß₁-ß₁-₂-ß₂-₃-COOH), the original ₁ globular domain (Segrest, J. P. et al. 1994. Arterioscler. Thromb. 14: 1674;–1685) is expanded to include residues 1;–1,000 and renamed the ß₁ domain. This change reflects the likelihood that the ß₁ domain, like lamprey lipovitellin, is a globular composite of -helical and ß-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 ß sheets of the ß₁ and ß₂ 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 ß 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 ₂ and ₃ 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 ßC 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.

Supplementary key words: amphipathic ß sheets, amphipathic -helices, cryoelectron microscopy, X-ray crystallography, boundary lipid, smectic phase, lipid phase transition, LDL receptor-binding domain

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