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Aromatic residues i...
Aromatic residues in the C terminus of apolipoprotein C-III mediate lipid binding and LPL inhibition
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Meyers, Nathan L. (författare)
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Larsson, Mikael (författare)
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- Vorrsjo, Evelina (författare)
- Umeå universitet,Fysiologisk kemi
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- Olivecrona, Gunilla (författare)
- Umeå universitet,Fysiologisk kemi
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Small, Donald M. (författare)
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(creator_code:org_t)
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 2017
- 2017
- Engelska.
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Ingår i: JOURNAL OF LIPID RESEARCH. - : AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. ; 58:5, s. 840-852
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Nyckelord
- lipoprotein lipase
- lipid and lipoprotein metabolism
- LDL/metabolism
- lipid/emulsions
- protein-lipid teraction
- surface pressure
- drop tensiometry
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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