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Cited by 345Lipoproteins and Cardiovascular HealthAlzheimer's disease research and treatmentsCholesterol and Lipid Metabolism

The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.

Structural basis for receptor binding heterogeneity of apolipoprotein E from type III hyperlipoproteinemic subjects.

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Rall, S C, Weisgraber, K H, Innerarity, T L, Mahley, R W·1982·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.79.15.4696PMC PMC346743
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Abstract

The three major isoforms of human apolipoprotein E (apo-E2, -E3, and -E4) are coded for by three alleles (epsilon 2, epsilon 3, and epsilon 4) which have a common genetic locus. Previously, we demonstrated that E2, E3, and E4 differ in primary structure from one another at two substitution sites, site A (residue 112) and site B (residue 158). At sites A/B, apo-E2, -E3, and -E4 contain cysteine/cysteine, cysteine/arginine, and arginine/arginine, respectively. We demonstrated that the substitution of cysteine for arginine at site B is at least partly responsible for the defective binding of apo-E2 to human fibroblast low density lipoprotein receptors, compared to the normal binding activity of apo-E3 or -E4. Subjects with the genetic disorder type III hyperlipoproteinemia are phenotypically homozygous for apo-E2, but the binding activity of apo-E to the fibroblast receptor differs considerably from one type III individual to another. We therefore undertook a partial comparative sequence analysis of apo-E2 from three type III subjects whose apo-E displayed this heterogeneity. The subject with the poorest binding apo-E2 was genotypically homozygous for an apo-E allele (epsilon 2); cysteine was found at sites A and B. The subject with the most active apo-E2 was genotypically homozygous for an apo-E allele (epsilon 2); cystine was found at site A and at a new site (site C, residue 145). The epsilon 2 allele specifies a protein that has arginine at site B (residue 158); the epsilon 2 allele specifies a protein that has arginine at site C (residue 145). Therefore, the two alleles differ from one another by cysteine/arginine interchanges at two positions, sites B and C. The third subject, whose apo-E2 displayed binding activity intermediate between the activities of the other two, was genotypically heterozygous, having one epsilon 2 allele and one epsilon 2 allele. The intermediate binding activity of apo-E2 from this subject resulted from having a mixture of severely defective apo-E (specified by epsilon 2) and slightly defective apo-E (specified by epsilon 2).

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Metadata

Authors
Rall, S. C., Weisgraber, K. H., Innerarity, T. L., & Mahley, R. W.
ORCID
Mahley, R W
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
1982-08
Volume
79
Issue
15
Pages
4696-4700
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.79.15.4696
PMC
PMC346743
OpenAlex
W2081151510
Cited by
345
References
16
Citations by year
2024: 7 · 2023: 2 · 2022: 5 · 2021: 5 · 2020: 3 · 2019: 3 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 6 · 2014: 4 · 2013: 3 · 2012: 7
FWCI
54.05
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
Keywords
apolipoprotein E, type III hyperlipoproteinemia, LDL receptor, apolipoprotein E isoforms, site-directed mutagenesis, receptor binding activity, genetic polymorphism
MeSH terms
Alleles, Amino Acid Sequence, Apolipoproteins, Apolipoproteins E, Genes, Humans, Hyperlipoproteinemia Type III, Receptors, Cell Surface, Low Density Lipoprotein Receptor-Related Protein-1

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