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Aromatic residues in the C terminus of apolipoprotein C-III mediate lipid binding and LPL inhibition
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
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2017 (English)In: JOURNAL OF LIPID RESEARCH, Vol. 58, no 5, 840-852 p.Article in journal (Refereed) Published
Abstract [en]

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.(jlr) 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 sub-strate.

Place, publisher, year, edition, pages
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC , 2017. Vol. 58, no 5, 840-852 p.
Keyword [en]
lipoprotein lipase, lipid and lipoprotein metabolism, LDL/metabolism, lipid/emulsions, protein-lipid teraction, surface pressure, drop tensiometry
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-136199DOI: 10.1194/jlr.M071126ISI: 000400479800004PubMedID: 28159869OAI: oai:DiVA.org:umu-136199DiVA: diva2:1120727
Available from: 2017-07-07 Created: 2017-07-07 Last updated: 2017-07-07Bibliographically approved

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CiteExportLink to record
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Cite
Citation style
  • apa
  • harvard1
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  • modern-language-association-8th-edition
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