ArticleAtherosclerosis2013
Allele-dependent thermodynamic and structural perturbations in ApoE variants associated with the correction of dyslipidemia and formation of spherical ApoE-containing HDL particles.
Article in Atherosclerosis, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
2 citing papers in PubMed, 3 citations in OpenAlex.
- Mercury Ion Binding to Apolipoprotein E Variants ApoE2, ApoE3, and ApoE4: Similar Binding Affinities but Different Structure Induction Effects.ACS omega · 2022Article
- Apolipoprotein E - A Multifunctional Protein with Implications in Various Pathologies as a Result of Its Structural Features.Computational and structural biotechnology journal · 2017Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
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 compared to wild-type. The presence of mutation only marginally affected the thermal stability of ApoE4 but greatly affected the thermal stability profile of ApoE2 leading to a previously uncharacterized intermediate stage. Both ApoE4mutC and ApoE2mutC were slightly stabilized against chemical denaturation compared to their wild-type counterparts. ApoE2mutC, in contrast to ApoE4mutC, exposed a larger hydrophobic surface to the solvent as determined by a fluorescent probe. Both mutants remodeled 1,2-dimyristoyl-sn-glycero-3-phosphocholine vesicles with identical kinetics to the wild-type proteins. Given the known conformational differences between ApoE2 and ApoE4, our findings suggest that the 261-265 region may be involved in inter-domain interactions within the ApoE molecule. Overall, we show that substitution of Leu261, Trp264 and Phe265 with Ala in ApoE2 leads to more pronounced perturbations of thermodynamic stability and structure than in ApoE4. The minimal perturbations in ApoE4mutC may make it a more suitable candidate for therapeutic applications for the correction of remnant removal disorders and atheroprotection.
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Registered trials
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