Structure of apolipoprotein B-100 in low density lipoproteins

There is general consensus that amphipathic alpha -helices and beta sheets represent the major lipid-associating motifs of apolipoprotein (apo)B-100. In this review, we examine the existing experimental and computational evid ence for the pentapartite domain structure of apoB. In the pentapartite nom enclature presented in this review (NH2-beta alpha (1)-beta (1)-alpha (2)-b eta (2)-alpha (3)-COOH), the original al globular domain (Segrest, J. P. et al. 1994. Artetioscler Thromb. 14: 1674-1685) is expanded to include resid ues 1-1,000 and renamed the beta alpha (1) domain. This change reflects the likelihood that the beta alpha (1) domain, like lamprey lipovitellin, is a globular composite of alpha -helical and beta -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 beta sheets of the beta (1) a nd beta (2) domains of apoB-100 are in direct contact with the neutral lipi d core of apoB-containing lipoproteins and play a role in core lipid organi zation. Evidence is also presented that these beta sheets largely determine LDL particle diameter. Analysis of published data shows that with a reduct ion in particle size, there is an increase in the number of amphipathic hel ices of the alpha (2) and alpha (3) domains associated with the surface lip ids of the LDL particle; these increases modulate the surface pressure decr eases caused by a reduction in radius of curvature. The properties of the L DL receptor-binding region within the overall domain structure of apoB-100 are also discussed. Finally, recent three-dimensional models of LDL obtaine d by cryoelectron microscopy and X-ray crystallography are discussed. These models show three common features: a semidiscoidal shape, a surface knob w ith the dimensions of the PC globular domain of lipovitellin, and planar mu ltilayers in the lipid core that are approximately 35 Angstrom apart; the m ultilayers are thought to represent cholesteryl ester in the smectic phase. These models present a conundrum: are LDL particles circulating at 37 degr eesC spheroidal in shape, as generally assumed, or are they semidiscoidal i n shape, as suggested by the models? The limited evidence available support s a spheroidal shape.