Allele-dependent thermodynamic and structural perturbations in ApoE variants associated with the correction of dyslipidemia and formation of spherical ApoE-containing HDL particles.

ABSTRACT: Overexpression of ApoE4[Leu261Ala/Trp264Ala/Phe265Ala] mutant (ApoE4mutC) prevents hypertriglyceridemia and promotes formation of spherical ApoE-containing HDL in ApoE(-/-) or ApoA-I(-/-) mice. Although, a similar phenotype was observed with ApoE2[Leu261Ala/Trp264Ala/Phe265Ala] (ApoE2mutC), small differences in cholesterol distribution to IDL/LDL, HDL2 and HDL3 fractions and ApoE distribution to HDL2 and HDL3 fractions suggested that ApoE allelic background can influence mutant ApoE properties. To understand the structural basis behind the properties of ApoE2mutC and ApoE4mutC variants we analyzed their structural and thermodynamic integrity in comparison to their wild-type counterparts. Circular dichroism spectroscopy revealed a significantly reduced helical content for both mutants compa

SUBMITTER: Georgiadou D 

PROVIDER: S-EPMC3546125 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature