These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Apolipoprotein A-I conformation in reconstituted discoidal lipoproteins varying in phospholipid and cholesterol content.
    Author: Bergeron J, Frank PG, Scales D, Meng QH, Castro G, Marcel YL.
    Journal: J Biol Chem; 1995 Nov 17; 270(46):27429-38. PubMed ID: 7499199.
    Abstract:
    The effects of the size and cholesterol content on the conformation of apolipoprotein A-I (apoA-I) have been studied in reconstituted discoidal lipoproteins containing two apoA-I per particle (Lp2A-I). The immunoreactivity of a series of 13 epitopes distributed along the apoA-I sequence has been evaluated in Lp2A-I with a phospholipid/apoA-I molar ratio ranging from 31 to 156 and in Lp2A-I with constant phospholipids but varying in cholesterol content from 0 to 22 molecules. The results are compatible with a three domain structure in apoA-I in which the central domain is located between residues 99 and 143 and postulated to be a hinged domain that responds differentially to changes in phospholipid and cholesterol contents. Increasing the phospholipid content results in significant changes of epitope immunoreactivity throughout the N-terminal and central domains of apoA-I with fewer modifications in the C-terminal domain. In contrast, increasing Lp2A-I of two central epitopes, A11 (residues 99-132) and 5F6 (residues 118-148), and an extreme N-terminal epitope, 4H1 (residues 2-8). Interestingly, the effects of increasing cholesterol or phospholipids on these epitopes are opposite. This suggests a specific effect of cholesterol on the central domain tertiary structure between residues 99 and 143. Competition binding assays among pairs of antibodies binding to apoA-I on Lp2A-I are best explained by invoking inter- as well as intramolecular competitions. The specificity of the intermolecular competitions suggests an N to C termini arrangement of the two apoA-I molecules around the disc. Increasing the phospholipid content of Lp2A-I mainly increases the competitions between 3G10 and antibodies binding to most adjacent epitopes. Simultaneously as Lp2A-I enlarges, several of these antibodies also enhance the binding of 3G10. This has been interpreted as evidence of a structural rearrangement of apoA-I as a result of the size increase where the alpha-helix (residues 99-121) that contains the 3G10 epitope is increasingly interacting with lipids resulting in the enhanced expression of this epitope. The increasing interactions of apoA-I helices with lipids in the enlarging disc are compatible with previous reports of a greater apoA-I stability in the large discs. By contrast, cholesterol has limited but specific effects on antibody competitions and decreases the interaction of the N-terminal domain with the domain containing 3G10, either by direct cholesterol protein interaction or by modification of the lipid phase packing.
    [Abstract] [Full Text] [Related] [New Search]