ArticleBiochemistry2008
Contributions of the carboxyl-terminal helical segment to the self-association and lipoprotein preferences of human apolipoprotein E3 and E4 isoforms.
Article in Biochemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 53 citations in OpenAlex.
- Cholesterol at the Center of Alzheimer's Disease: A Unifying Hypothesis on the Pathogenic Mechanism.Molecules (Basel, Switzerland) · 2026Review
- Conformational features of guinea pig apolipoprotein E offer insights into functioning of human apolipoprotein E.Archives of biochemistry and biophysics · 2025Article
- Unraveling APOE4's Role in Alzheimer's Disease: Pathologies and Therapeutic Strategies.Current protein & peptide science · 2025Review
- Apolipoprotein E in lipid metabolism and neurodegenerative disease.Trends in endocrinology and metabolism: TEM · 2023Review
- Isoform-specific modification of apolipoprotein E by 4-hydroxynonenal: protective role of apolipoprotein E3 against oxidative species.The FEBS journal · 2023Article
- Insights into the C-terminal domain of apolipoprotein E from chimera studies with apolipophorin III.Molecular and cellular biochemistry · 2023Article
- The LDL receptor binding domain of apolipoprotein E directs the relative orientation of its C-terminal segment in reconstituted nascent HDL.Biochimica et biophysica acta. Biomembranes · 2021Article
- APOE in the normal brain.Neurobiology of disease · 2020Review
- O-glycosylation on cerebrospinal fluid and plasma apolipoprotein E differs in the lipid-binding domain.Glycobiology · 2020Article
- Conformational analysis of apolipoprotein E3/E4 heteromerization.The FEBS journal · 2019Article
- The serine protease HtrA1 contributes to the formation of an extracellular 25-kDa apolipoprotein E fragment that stimulates neuritogenesis.The Journal of biological chemistry · 2018Article
- Helical structure, stability, and dynamics in human apolipoprotein E3 and E4 by hydrogen exchange and mass spectrometry.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Mechanism of Lipid Binding of Human Apolipoprotein E3 by Hydrogen/Deuterium Exchange/Mass Spectrometry and Fluorescence Polarization.Protein and peptide letters · 2016Article
- Fluorescence study of domain structure and lipid interaction of human apolipoproteins E3 and E4.Biochimica et biophysica acta · 2014Article
- Influence of domain stability on the properties of human apolipoprotein E3 and E4 and mouse apolipoprotein E.Biochemistry · 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
- The roles of C-terminal helices of human apolipoprotein A-I in formation of high-density lipoprotein particles.Biochimica et biophysica acta · 2014Article
- Molecular mechanisms responsible for the differential effects of apoE3 and apoE4 on plasma lipoprotein-cholesterol levels.Arteriosclerosis, thrombosis, and vascular biology · 2013Article
- Interactions of apolipoprotein A-I with high-density lipoprotein particles.Biochemistry · 2013Article
- Biochemical and biophysical characterization of recombinant rat apolipoprotein E: similarities to human apolipoprotein E3.Archives of biochemistry and biophysics · 2013Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
To understand the molecular basis for the different self-association and lipoprotein preferences of apolipoprotein (apo) E isoforms, we compared the effects of progressive truncation of the C-terminal domain in human apoE3 and apoE4 on their lipid-free structure and lipid binding properties. A VLDL/HDL distribution assay demonstrated that apoE3 binds much better than apoE4 to HDL 3, whereas both isoforms bind similarly to VLDL. Removal of the C-terminal helical regions spanning residues 273-299 weakened the ability of both isoforms to bind to lipoproteins; this led to the elimination of the isoform lipoprotein preference, indicating that the C-terminal helices mediate the lipoprotein selectivity of apoE3 and apoE4 isoforms. Gel filtration chromatography experiments demonstrated that the monomer-tetramer distribution is different for the two isoforms with apoE4 being more monomeric than apoE3 and that removal of the C-terminal helices favors the monomeric state in both isoforms. Consistent with this, fluorescence measurements of Trp-264 in single-Trp mutants revealed that the C-terminal domain in apoE4 is less organized and more exposed to the aqueous environment than in apoE3. In addition, the solubilization of dimyristoylphosphatidylcholine multilamellar vesicles is more rapid with apoE4 than with apoE3; removal of the C-terminal helices significantly affected solubilization rates with both isoforms. Taken together, these results indicate that the C-terminal domain is organized differently in apoE3 and apoE4 so that apoE4 self-associates less and binds less than apoE3 to HDL surfaces; these alterations may lead to the pathological sequelae for cardiovascular and neurodegenerative diseases.
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