Nascent high density lipoproteins formed by ABCA1 resemble lipid rafts and are structurally organized by three apoA-I monomers. J Lipid Res 2012 Sep;53(9):1890-909
Date
07/04/2012Pubmed ID
22750655Pubmed Central ID
PMC3413229DOI
10.1194/jlr.M026674Scopus ID
2-s2.0-84864851111 (requires institutional sign-in at Scopus site) 101 CitationsAbstract
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.
Author List
Sorci-Thomas MG, Owen JS, Fulp B, Bhat S, Zhu X, Parks JS, Shah D, Jerome WG, Gerelus M, Zabalawi M, Thomas MJAuthors
Mary Sorci Thomas PhD Professor in the Medicine department at Medical College of WisconsinMichael J. Thomas PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
ATP Binding Cassette Transporter 1ATP-Binding Cassette Transporters
Apolipoprotein A-I
Biological Transport
Ceramides
Cholesterol
Fatty Acids
HEK293 Cells
Humans
Lipoproteins, HDL
Membrane Microdomains
Protein Conformation
Sphingomyelins
