The receptor-binding domain of human apolipoprotein E. Monoclonal antibody inhibition of binding.
Open accessAbstract
To investigate the potential of monoclonal antibodies as probes to determine the receptor-binding domain of apolipoprotein E (apo-E), five apo-E antibodies were tested to see if any of them inhibited 125I-apo-E3 . dimyristoylphosphatidylcholine binding to apo-B,E receptors on cultured fibroblasts. Only one of the five antibodies, referred to as 1D7, was found to inhibit binding, blocking greater than 90% of the receptor-binding activity of apo-E3 dimyristoylphosphatidyl-choline. The 1D7 Fab fragments were also effective inhibitors. The 1D7 bound to a Mr = 22,000 NH2-terminal thrombolytic fragment of apo-E (residues 1-191) and to a 93-residue cyanogen bromide fragment of apo-E (residues 126-218). The four noninhibitory antibodies bound only to the NH2-terminal thrombolytic fragment. These results suggested that the 1D7 epitope is contained between residues 126 and 191, and that the epitopes of the other antibodies are not contained in this region. The use of synthetic apo-E fragments, which cover various lengths of the sequence from residues 129-169, and human apo-E variants with substitutions at residues 145, 146, or 158, narrowed the location of the 1D7 epitope to residues 139-169 and, most likely, to the immediate vicinity of residues 140-150. It is of interest that 1D7 was found to bind to the same region of apo-E that has been implicated as the receptor-binding domain in receptor-binding studies using human apo-E variants and apo-E3 fragments.
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The receptor-binding domain of apo E lies between residues 140 and 150.
“The determination of receptor-binding affinity of known variants (6,13,14,(19)(20)(21), and the blocking ofreceptor binding by monoclonal antibodies to apo E (22) have established that its receptor-binding domain lies between residues 140 and 150.”
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 [22]
Secondary structure predictions suggest that position 136 lies in an alpha-helix from residues 130 to 150, which includes the receptor-binding domain from 140 to 150.
“Secondary structure predictions (54,55) suggest that position 136 is part of an a-helix that extends between residues 130 and 150 (13,24), encompassing the receptor-binding domain from 140 to 150 (22).”
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 [22]
Cites
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New Insights into the Heparan Sulfate Proteoglycan-binding Activity of Apolipoprotein E
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- Authors
- Weisgraber, K. H., Innerarity, T. L., Harder, K. J., 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
- 1983-10
- Volume
- 258
- Issue
- 20
- Pages
- 12348-12354
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1576642143
- Cited by
- 220
- References
- 3
- Citations by year
- 2025: 1 · 2022: 1 · 2020: 2 · 2019: 1 · 2017: 1 · 2015: 2 · 2014: 6 · 2013: 4
- FWCI
- 17.33
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- 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 E, receptor binding domain, epitope mapping, Fab fragment
- MeSH terms
- Amino Acid Sequence, Animals, Antibodies, Monoclonal, Antigen-Antibody Complex, Apolipoproteins, Apolipoproteins E, Cells, Cultured, Dogs, Fibroblasts, Humans, Infant, Newborn, Kinetics, Lipoproteins, LDL, Male, Receptors, Cell Surface, Receptors, LDL, Skin, Species Specificity, Rats
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