ORBi: Liu Hq. - Characterization Of The Lipid-Binding Properties And Lipoprotein Lipase Inhibition Of A Novel Apolipoprotein C-Iii Variant Ala23thr

Reference : Characterization Of The Lipid-Binding Properties And Lipoprotein Lipase Inhibition Of A ...


	Document type :	Scientific journals : Article
	Discipline(s) :	Life sciences : Biochemistry, biophysics & molecular biology
	To cite this reference:	http://hdl.handle.net/2268/63661

Title :	Characterization Of The Lipid-Binding Properties And Lipoprotein Lipase Inhibition Of A Novel Apolipoprotein C-Iii Variant Ala23thr
Language :	English
Author, co-author :	Liu, Hq. [> > > >]
	Labeur, C. [> > > >]
	Xu, Cf. [> > > >]
	Ferrell, R. [> > > >]
	Lins, Laurence [Université de Liège > > Gembloux Agro-Bio Tech >]
	Brasseur, Robert [Université de Liège > > Gembloux Agro-Bio Tech >]
	Rosseneu, M. [> > > >]
	Weiss, Km. [> > > >]
	Humphries, Se. [> > > >]
	Talmud, Pj. [> > > >]
Publication date :	2000
Journal title :	Journal of Lipid Research
Volume :	41
Issue/season :	11
Pages :	9201-12
Audience :	International
ISSN :	0022-2275
Abstract :	[en] The physicochemical properties of recombinant wild type and three site-directed mutants of apolipoprotein C-III (apoC-III), designed by molecular modeling to alter specific amino acid residues implicated in lipid binding (L9T/T20L, F64A/W65A) or LPL inhibition (K21A), were compared. Relative lipid binding efficiencies to dimyristoylphosphatidylcholine (DMPC) were L9T/T20L > WT >K21A > F64A/W65A with an inverse correlation with size of the discoidal complexes formed. Physicochemical analysis (Trp fluorescence, circular dichroism, and GdnHCl denaturation) suggests that L9T/T20L forms tighter and more stable lipid complexes with phospholipids, while F64A/W65A associates less tightly. Lipid displacement properties were tested by gel-filtrating apoE:dipalmitoylphosphatidylcholine (DPPC) discoidal complexes mixed with the various apoC-III variants. All apoC-III proteins bound to the apoE:DPPC complexes; the amount of apoE displaced from the complex was dependent on the apoC-III lipid binding affinity. All apoC-III proteins inhibited LPL in the presence or absence of apoC-II, with F64A/W65A displaying the most inhibition, suggesting that apoC-III inhibition of LPL is independent of lipid binding and therefore of apoC-II displacement. Taken together. these data suggest that the hydrophobic residues F64 and W65 are crucial for the lipid binding properties of apoC-III and that redistribution of the N-terminal helix of apoC-III (L9T/T20L) enhances the stability of the lipid-bound protein, while LPL inhibition by apoC-III is likely to be due to protein:protein interactions.
Target :	Researchers ; Professionals
Permalink :	http://hdl.handle.net/2268/63661

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