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Aromatic residues in the C terminus of apolipoprotein C-III mediate lipid binding and LPL inhibition.
- Source :
-
Journal of lipid research [J Lipid Res] 2017 May; Vol. 58 (5), pp. 840-852. Date of Electronic Publication: 2017 Feb 03. - Publication Year :
- 2017
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Abstract
- Plasma apoC-III levels correlate with triglyceride (TG) levels and are a strong predictor of CVD outcomes. ApoC-III elevates TG in part by inhibiting LPL. ApoC-III likely inhibits LPL by competing for lipid binding. To probe this, we used oil-drop tensiometry to characterize binding of six apoC-III variants to lipid/water interfaces. This technique monitors the dependence of lipid binding on surface pressure, which increases during TG hydrolysis by LPL. ApoC-III adsorption increased surface pressure by upward of 18 mN/m at phospholipid/TG/water interfaces. ApoC-III was retained to high pressures at these interfaces, desorbing at 21-25 mN/m. Point mutants, which substituted alanine for aromatic residues, impaired the lipid binding of apoC-III. Adsorption and retention pressures decreased by 1-6 mN/m in point mutants, with the magnitude determined by the location of alanine substitutions. Trp42 was most critical to mediating lipid binding. These results strongly correlate with our previous results, linking apoC-III point mutants to increased LPL binding and activity at lipid surfaces. We propose that aromatic residues in the C-terminal half of apoC-III mediate binding to TG-rich lipoproteins. Increased apoC-III expression in the hypertriglyceridemic state allows apoC-III to accumulate on lipoproteins and inhibit LPL by preventing binding and/or access to substrate.<br /> (Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.)
Details
- Language :
- English
- ISSN :
- 1539-7262
- Volume :
- 58
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of lipid research
- Publication Type :
- Academic Journal
- Accession number :
- 28159869
- Full Text :
- https://doi.org/10.1194/jlr.M071126