Identification of the disulfide-linked homodimer of apolipoprotein E3 in plasma. Impact on receptor binding activity
Open accessAbstract
The nature of disulfide-linked structures of apolipoprotein (apo) E3 in the plasma of E3/3 subjects was examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis performed under nonreducing conditions followed by immunoblotting with apoE-specific antibodies. In addition to the expected presence of the heterodimer apoE3-A-II and monomeric apoE3, a band with an apparent Mr approximately 100,000 was also observed in plasma that had been treated with sulfhydryl-trapping reagents. This band and apoE3-A-II were both eliminated by disulfide reduction, which produced a corresponding increase in monomeric apoE3. Both bands were absent in plasma from a subject with the E4/4 phenotype. In spite of its apparent molecular weight on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the high molecular weight band was demonstrated to represent the disulfide-linked homodimer of apoE3. It was isolated from purified apoE3 preparations that had undergone oxygen-mediated dimerization and shown to elute from a Sephacryl S-300 column in a position with the expected molecular weight of a homodimer. The apoE3 dimer displayed a preference for high density lipoproteins, as determined by agarose chromatography of E3/3 plasma but was stripped from high density lipoproteins by ultracentrifugation. Quantitation of the relative ratios of homodimer, apoE3-A-II, and monomer in the plasma of 22 normolipidemic E3/3 subjects by immunoblotting revealed that the disulfide-linked structures acc…
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The western blot under reducing conditions showed complete breakdown of apoE homodimers and heterodimers, consistent with previous literature.
“In contrast, the western under reducing conditions show a complete breakdown of the apoE homodimers and heterodimers (Fig. 2), consistent with previous literature [35].”
From Discovery of a Missense Mutation (Q222K) of the <i>APOE</i> Gene from the Australian Imaging, Biomarker and Lifestyle Study (2023) · cites this paper as [35]
The apoE-apoAII complex occurs in ɛ2 and ɛ3 carriers but not ɛ4/ɛ4 homozygotes.
“this complex has been shown to occur in ɛ2 and ɛ3 carriers but not ɛ4/ ɛ4 homozygotes [35].”
From Discovery of a Missense Mutation (Q222K) of the <i>APOE</i> Gene from the Australian Imaging, Biomarker and Lifestyle Study (2023) · cites this paper as [35]
The self-association measured here is distinct from the cysteine-dependent disulfide-linked dimers of ApoE that have been described in plasma and CSF.
“It is important to note that the self-association measured here is distinct from the cysteinedependent disulfide-linked dimers of ApoE that have been described in plasma and CSF (32,43).”
From APOE Isoform-Dependent Self-Association Measured by a Split-Luciferase Complementation Assay: Differential Effects of Disease-Risk and Protective Variants (2026) · cites this paper as [32]
Cysteine-dependent disulfide-linked ApoE species are unique to ApoE3 and ApoE2, which carry cysteine residues at position 112 and/or 158, and cannot form in ApoE4.
“Those disulfide-linked species are unique to ApoE3 and ApoE2, which carry cysteine residues at position 112 and/or 158, and cannot form in ApoE4.”
From APOE Isoform-Dependent Self-Association Measured by a Split-Luciferase Complementation Assay: Differential Effects of Disease-Risk and Protective Variants (2026) · cites this paper as [32]
Common polymorphisms of human apoE (apoE2, -E3, and -E4) influence lipid metabolism due to differences in receptor binding activity and lipoprotein association preference.
“Common polymorphisms of human apoE (apoE2, -E3, and -E4) infl uence lipid metabolism due to differences in receptor binding activity and lipoprotein association preference (5)(6)(7)(8)(9).”
From Macrophage-derived apoESendai suppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice (2014) · cites this paper as [8]
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- Authors
- Weisgraber, K. H., & Shinto, L. H.
- Affiliations
- University of California, San Francisco (US)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1991-06
- Volume
- 266
- Issue
- 18
- Pages
- 12029-12034
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1495814806
- Cited by
- 104
- References
- 4
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 2 · 2023: 4 · 2022: 5 · 2021: 1 · 2020: 3 · 2019: 3 · 2018: 1 · 2017: 4 · 2016: 2 · 2014: 2 · 2013: 3 · 2012: 2
- FWCI
- 8.07
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL-41633, P01HL041633)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- apolipoprotein E3, disulfide-linked homodimer, receptor binding activity, high-density lipoprotein, sulfhydryl reagents, lipoprotein metabolism
- MeSH terms
- Apolipoproteins E, Binding, Competitive, Chromatography, Gel, Disulfides, Electrophoresis, Polyacrylamide Gel, Humans, Phenotype, Radioligand Assay, Receptors, LDL, Sulfhydryl Compounds, Tumor Cells, Cultured, Blotting, Western, Culture Techniques
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