Human apolipoprotein E. Determination of the heparin binding sites of apolipoprotein E3.
Open accessAbstract
The interaction of human apolipoprotein (apo-) E3 with heparin was examined using heparin-Sepharose as a model system. The approach taken to determine the region of apo-E that is responsible for binding to heparin was to identify apo-E monoclonal antibodies that inhibited heparin binding, to determine the epitopes of the inhibiting antibodies, and finally to examine the heparin binding of fragments containing the inhibiting antibody epitopes. Three antibodies, designated 1D7, 6C5, and 3H1, were found to inhibit binding, suggesting that multiple heparin binding sites were present on apo-E. The epitopes of the inhibiting antibodies were determined by immunoblot analysis of synthetic or proteolytic fragments of apo-E. Measurement of the heparin binding activity of fragments containing epitopes of the inhibiting antibodies demonstrated that apo-E3 contains two heparin binding sites. The first site is located in the vicinity of residues 142-147 and coincides with the 1D7 epitope. The second binding site is contained in the carboxyl-terminal region of apo-E and is inhibited by 3H1, the epitope of which is located between residues 243 and 272. The epitope of the third inhibiting antibody, 6C5, is located at the amino terminus of apo-E; however, this antibody inhibits the second heparin binding site located in the carboxyl-terminal region. A head-to-tail association of apo-E, in which the 6C5 epitope and the second heparin binding site would be in close proximity, is proposed to account for this observation. In the lipid-free state both heparin binding sites on apo-E are expressed; however, when apo-E is complexed to phospholipid or on the surface of a lipoprotein particle, only the first binding site (residues 142-147) is expressed.
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The heparin-binding and receptor-binding domains coincide.
“This is significant because the heparin-binding and receptor-binding domains coincide (59).”
From Apolipoprotein E2-Christchurch (136 Arg----Ser). New variant of human apolipoprotein E in a patient with type III hyperlipoproteinemia. (1987) · cites this paper as [59]
Heparin binding sites are located in both the N-terminal and the C-terminal domains; the heparin binding site in the N-terminal domain is located at residues 142-147, which overlaps with the LDL receptor binding region.
“Meanwhile, heparin binding sites are located in both the N-terminal and the C-terminal domains; the heparin binding site in the N-terminal domain is located at residues 142–147, which overlaps with the LDL receptor binding region12).”
From Impact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features (2025) · cites this paper as [12]
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- Authors
- Weisgraber, K. H., Rall, S. C., Mahley, R. W., Milne, R. W., Marcel, Y. L., & Sparrow, J. T.
- Affiliations
- University of California, San Francisco (US)
- ORCID
- Mahley, R W
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1986-02
- Volume
- 261
- Issue
- 5
- Pages
- 2068-2076
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1505230657
- Cited by
- 240
- References
- 5
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 1 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 3 · 2015: 3 · 2014: 2 · 2013: 3 · 2012: 3
- FWCI
- 11.49
- 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 30064)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- apolipoprotein E3, heparin-binding site, heparin binding, monoclonal antibodies, epitope mapping, C-terminal region, amino-terminal region, phospholipid complex
- MeSH terms
- Animals, Antibodies, Monoclonal, Epitopes, Apolipoproteins E, Binding Sites, Binding, Competitive, Dogs, Heparin, Humans, Lipoproteins, HDL, Peptide Fragments, Sepharose
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