ArticlePloS one2011
Biophysical analysis of apolipoprotein E3 variants linked with development of type III hyperlipoproteinemia.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 2 of them syntheses that pooled it.
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Who cites it
14 citing papers in PubMed, 2 syntheses or guidelines pooled it, 21 citations in OpenAlex.
- Association of apoE gene polymorphisms with lipid metabolism in renal diseases.African health sciences · 2020Pooled it
- Association of apoE gene expression and its gene polymorphism with nephrotic syndrome susceptibility: a meta-analysis of experimental and human studies.Molecular biology reports · 2012Pooled it
- Astrocytic APOE3-Christchurch expression ameliorates brain amyloid-β pathology in 5xFAD mice.Translational psychiatry · 2026Article
- ApoE3 R136S binds to Tau and blocks its propagation, suppressing neurodegeneration in mice with Alzheimer's disease.Neuron · 2025Article
- Knockout rat models mimicking human atherosclerosis created by Cpf1-mediated gene targeting.Scientific reports · 2019Article
- Thermodynamic destabilization and aggregation propensity as the mechanism behind the association of apoE3 mutants and lipoprotein glomerulopathy.Journal of lipid research · 2018Article
- Apolipoprotein E deficiency accelerates atherosclerosis development in miniature pigs.Disease models & mechanisms · 2018Article
- CRISPR/Cas9-mediated ApoE-/- and LDLR-/- double gene knockout in pigs elevates serum LDL-C and TC levels.Oncotarget · 2017Article
- The ability of apolipoprotein E fragments to promote intraneuronal accumulation of amyloid beta peptide 42 is both isoform and size-specific.Scientific reports · 2016Article
- Fluorescence study of domain structure and lipid interaction of human apolipoproteins E3 and E4.Biochimica et biophysica acta · 2014Article
- Molecular basis for increased risk for late-onset Alzheimer disease due to the naturally occurring L28P mutation in apolipoprotein E4.The Journal of biological chemistry · 2014Article
- A possible structural basis behind the pathogenic role of apolipoprotein E hereditary mutations associated with lipoprotein glomerulopathy.Clinical and experimental nephrology · 2014Review
- Allele-dependent thermodynamic and structural perturbations in ApoE variants associated with the correction of dyslipidemia and formation of spherical ApoE-containing HDL particles.Atherosclerosis · 2013Article
- Thermodynamic and structural destabilization of apoE3 by hereditary mutations associated with the development of lipoprotein glomerulopathy.Journal of lipid research · 2013Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundApolipoprotein E (apoE) is a major protein of the lipoprotein transport system that plays important roles in lipid homeostasis and protection from atherosclerosis. ApoE is characterized by structural plasticity and thermodynamic instability and can undergo significant structural rearrangements as part of its biological function. Mutations in the 136-150 region of the N-terminal domain of apoE, reduce its low density lipoprotein (LDL) receptor binding capacity and have been linked with lipoprotein disorders, such as type III hyperlipoproteinemia (HLP) in humans. However, the LDL-receptor binding defects for these apoE variants do not correlate well with the severity of dyslipidemia, indicating that these variants may carry additional properties that contribute to their pathogenic potential. METHODOLOGY/PRINCIPAL
findingsIn this study we examined whether three type III HLP predisposing apoE3 variants, namely R136S, R145C and K146E affect the biophysical properties of the protein. Circular dichroism (CD) spectroscopy revealed that these mutations do not significantly alter the secondary structure of the protein. Thermal and chemical unfolding analysis revealed small thermodynamic alterations in each variant compared to wild-type apoE3, as well as effects in the reversibility of the unfolding transition. All variants were able to remodel multillamelar 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) vesicles, but R136S and R145C had reduced kinetics. Dynamic light scattering analysis indicated that the variant R136S exists in a higher-order oligomerization state in solution. Finally, 1-anilinonaphthalene-8-sulfonic acid (ANS) binding suggested that the variant R145C exposes a larger amount of hydrophobic surface to the solvent. CONCLUSIONS/SIGNIFICANCE: Overall, our findings suggest that single amino acid changes in the functionally important region 136-150 of apoE3 can affect the molecule's stability and conformation in solution and may underlie functional consequences. However, the magnitude and the non-concerted nature of these changes, make it unlikely that they constitute a distinct unifying mechanism leading to type III HLP pathogenesis.
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