Nascent high density lipoproteins formed by ABCA1 resemble lipid rafts and are structurally organized by three apoA-I monomers.

Sorci-Thomas MG, Owen JS, Fulp B, Bhat S, Zhu X, Parks JS, Shah D, Jerome WG, Gerelus M, Zabalawi M, Thomas MJ
J Lipid Res. 2012 53 (9): 1890-909

PMID: 22750655 · PMCID: PMC3413229 · DOI:10.1194/jlr.M026674

This report details the lipid composition of nascent HDL (nHDL) particles formed by the action of the ATP binding cassette transporter A1 (ABCA1) on apolipoprotein A-I (apoA-I). nHDL particles of different size (average diameters of ∼ 12, 10, 7.5, and <6 nm) and composition were purified by size-exclusion chromatography. Electron microscopy suggested that the nHDL were mostly spheroidal. The proportions of the principal nHDL lipids, free cholesterol, glycerophosphocholine, and sphingomyelin were similar to that of lipid rafts, suggesting that the lipid originated from a raft-like region of the cell. Smaller amounts of glucosylceramides, cholesteryl esters, and other glycerophospholipid classes were also present. The largest particles, ∼ 12 nm and 10 nm diameter, contained ∼ 43% free cholesterol, 2-3% cholesteryl ester, and three apoA-I molecules. Using chemical cross-linking chemistry combined with mass spectrometry, we found that three molecules of apoA-I in the ∼ 9-14 nm nHDL adopted a belt-like conformation. The smaller (7.5 nm diameter) spheroidal nHDL particles carried 30% free cholesterol and two molecules of apoA-I in a twisted, antiparallel, double-belt conformation. Overall, these new data offer fresh insights into the biogenesis and structural constraints involved in forming nascent HDL from ABCA1.

MeSH Terms (13)

Apolipoprotein A-I ATP-Binding Cassette Transporters ATP Binding Cassette Transporter 1 Biological Transport Ceramides Cholesterol Fatty Acids HEK293 Cells Humans Lipoproteins, HDL Membrane Microdomains Protein Conformation Sphingomyelins

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