Reference : Characterization Of The Lipid-Binding Properties And Lipoprotein Lipase Inhibition Of A ...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/63661
Characterization Of The Lipid-Binding Properties And Lipoprotein Lipase Inhibition Of A Novel Apolipoprotein C-Iii Variant Ala23thr
English
Liu, Hq. [> > > >]
Labeur, C. [> > > >]
Xu, Cf. [> > > >]
Ferrell, R. [> > > >]
Lins, Laurence mailto [Université de Liège > > Gembloux Agro-Bio Tech >]
Brasseur, Robert mailto [Université de Liège > > Gembloux Agro-Bio Tech >]
Rosseneu, M. [> > > >]
Weiss, Km. [> > > >]
Humphries, Se. [> > > >]
Talmud, Pj. [> > > >]
2000
Journal of Lipid Research
41
11
9201-12
Yes (verified by ORBi)
International
0022-2275
[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.
Researchers ; Professionals
http://hdl.handle.net/2268/63661

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