Human E apoprotein heterogeneity. Cysteine-arginine interchanges in the amino acid sequence of the apo-E isoforms.
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The abbreviations used are: apo-E, E apoprotein; VLDL, very low density lipoproteins; E isoforms, E-1, E-2, E-3, and E-4, using the onedimensional gel nomenclature established by Utermann et al. (17).Equivalency of the Zannis and Breslow (20) nomenclature with the Utermann system: p-11 pattern, E-4/E-4 genotype; p-111 pattern, E-3/E-3 genotype; D-IV pattern, E-2/E-2 genotype; a-I1 pattern, E-4/E-3 genotype; a-111 pattern, E-3/E-2 genotype; a-IV pattern, E-4/E-2 genotype.and several different animals (5-10).Metabolically, this Mr ' Expressed as residues per mole, assuming Ala = 1.0 (2 determinations).Converted to homoserine and homoserine lactone, which were present in all of these hydrolysates.Determined as cysteic acid.
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Cysteamine adds a positive charge to cysteine residues, and the modified apo E has an altered isoelectric focusing pattern.
“This reagent adds a positive charge to cysteine residues and the resultant modified apo E has an altered pattern on isoelectric focusing (12).”
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 [12]
Three apo E2 variants have been described, each differing from apo E3 by a single amino acid substitution.
“Three variants ofapo E2 have been described.Each ofthese differs from apo E3 by a single amino acid substitution (6, 12- 14).”
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 [12]
APOE gene analysis showed both codons 112 and 158 had cysteine, indicating apoE2/E2.
“Both codons 112 and 158 showed the amino acid cysteine (Cys) (shown in Fig. 3), which indicated that the isoform of apoE was apoE2/E2 [8, 9].”
The gel filtration separation profile of the CNBr peptides of apoE3-Leiden is similar to that for normal apoE3 except for the presence of a new peak (CBX) eluting at the column volume.
“This profile is similar to that for normal apoE3 (17, 23) except for the presence of a new peak (CBX) eluting at the column volume.”
From Apolipoprotein E3-Leiden contains a seven-amino acid insertion that is a tandem repeat of residues 121–127 (1989) · cites this paper as [17]
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Zannis, V. I., & Breslow, J. L. (1981) · Biochemistry · doi:10.1021/bi00507a059 · Cited by 563 · see citing works
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Gustavsson, J., Mehlig, K., Leander, K., Strandhagen, E., Björck, L., Thelle, D. S., Lissner, L., Blennow, K., Zetterberg, H., & Nyberg, F. (2012) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2011.10.011 · Cited by 41 · see citing works
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Clément-Collin, V., Barbier, A., Dergunov, A. D., Visvikis, A., Siest, G., Desmadril, M., Takahashi, M., & Aggerbeck, L. P. (2006) · Biophysical Chemistry · doi:10.1016/j.bpc.2005.07.009 · Cited by 32 · see citing works
FEUSSNER, G., FUNKE, H., WENG, W., ASSMANN, G., LACKNER, K. J., & ZIEGLER, R. (1992) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.1992.tb01511.x · Cited by 28 · see citing works
Mann, W. A., Lohse, P., Gregg, R. E., Ronan, R., Hoeg, J. M., Zech, L. A., & Brewer, H. B. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118096 · Cited by 28 · see citing works
Okoro, E. U., Zhao, Y., Guo, Z., Zhou, L., Lin, X., & Yang, H. (2012) · PLoS ONE · doi:10.1371/journal.pone.0044430 · Cited by 25 · see citing works
Feussner, G., Scharnagl, H., Scherbaum, C., Acar, J., Dobmeyer, J., Lohrmann, J., Wieland, H., & März, W. (1996) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)39106-9 · Cited by 21 · see citing works
Koshino, A., Takaeda, C., Matsuno, T., Kitajima, S., Iwata, Y., Sakai, N., Nagahama, K., Niida, Y., Saito, T., Yokoyama, H., et al. (2022) · Case Reports in Nephrology and Dialysis · doi:10.1159/000525086 · Cited by 2 · see citing works
Jackson, R. J., Dierksmeier, S., Nishtar, M., Meltzer, J., Balduin, F., Beaumont, B., Fan, Z., Sergienko, E., Olson, S., Jackson, M. R., et al. (2026) · doi:10.64898/2026.06.09.730809
- Authors
- Weisgraber, K. H., Rall, S. C., & Mahley, R. W.
- Affiliations
- Gladstone Institutes (US)
- ORCID
- Mahley, R W
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1981-09
- Volume
- 256
- Issue
- 17
- Pages
- 9077-9083
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1546262989
- Cited by
- 777
- References
- 1
- Citations by year
- 2026: 15 · 2025: 24 · 2024: 13 · 2023: 16 · 2022: 16 · 2021: 17 · 2020: 12 · 2019: 13 · 2018: 16 · 2017: 22 · 2016: 14 · 2015: 22 · 2014: 24 · 2013: 19 · 2012: 21
- FWCI
- 62.12
- 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 › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- apolipoprotein E, amino acid sequence variation, protein heterogeneity, VLDL, genetic polymorphism, cysteic acid, homoserine lactone, homoserine
- MeSH terms
- Alleles, Amino Acid Sequence, Apolipoproteins, Apolipoproteins E, Arginine, Cysteine, Homozygote, Humans, Isomerism, Lipoproteins, VLDL, Peptide Fragments
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