Three-dimensional structure of the LDL receptor-binding domain of the human apolipoprotein E2 (Arg136 → Cys) variant

Feussner, Giso; Albanese, Marco; Valencia, Alfonso

doi:10.1016/0021-9150(96)05870-4

Cited by 7Lipoproteins and Cardiovascular HealthLipid metabolism and disordersCholesterol and Lipid Metabolism

Three-dimensional structure of the LDL receptor-binding domain of the human apolipoprotein E2 (Arg136 → Cys) variant

Feussner, Giso, Albanese, Marco, Valencia, Alfonso·1996·Atherosclerosis

DOI 10.1016/0021-9150(96)05870-4

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Abstract

The familial lipoprotein disorder type III hyperlipoproteinemia (HLP) is usually inherited as a recessive trait. Indeed, more than 90% of affected individuals are homozygous for a receptor binding-defective isoform of apolipoprotein (apo) E, apo E2. However, some rare apo E variants have been described that dominantly (thus in a single dose) predispose to the disease. Amino acid substitutions, which are accompanied with the loss of positive charges within the proposed apo E binding-region to lipoprotein receptors, seem to be responsible in most of these cases for the dominance with respect to the expression of type III HLP. So far available data in the literature on the naturally occurring human apo E2 (Arg136-->Cys) variant are not conclusive about its recessive or dominant character. We recently identified a subject heterozygous for this mutation, presenting the typical clinical and biochemical characteristics of type III HLP. In the present study we performed further analysis of the mutation on apo E structure and function based on computer modeling. Our combined data point to a dominant influence of the apo E2 (Arg136-->Cys) variant with respect to the transmission of the disease.

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From Exceptionally low likelihood of Alzheimer’s dementia in APOE2 homozygotes from a 5,000-person neuropathological study (2020) · cites this paper as [15]
A targeted antibody can lower wild-type ApoE3 binding.
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From Exceptionally low likelihood of Alzheimer’s dementia in APOE2 homozygotes from a 5,000-person neuropathological study (2020) · cites this paper as [15]

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The functional characteristics of a human apolipoprotein E variant (cysteine at residue 142) may explain its association with dominant expression of type III hyperlipoproteinemia
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Rall, S. C., Newhouse, Y. M., Clarke, H. R., Weisgraber, K. H., McCarthy, B. J., Mahley, R. W., & Bersot, T. P. (1989) · Journal of Clinical Investigation · doi:10.1172/jci113988 · Cited by 103 · see citing works
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Self-citation

Authors: Feussner, G., Albanese, M., & Valencia, A.
Affiliations: University Hospital Heidelberg (DE)
European Molecular Biology Laboratory (DE)
ORCID: Valencia, Alfonso
Venue: Atherosclerosis
Publisher: Elsevier BV
Published: 1996-10
Volume: 126
Issue: 2
Pages: 177-184
ISSN: 0021-9150 (ISSN-L)
DOI: 10.1016/0021-9150(96)05870-4
OpenAlex: W1981437877
Cited by: 7
References: 32
Citations by year: 2024: 1 · 2021: 1 · 2020: 2 · 2014: 1
FWCI: 0.00
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Atherosclerosis (publishedVersion)
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 E2, type III hyperlipoproteinemia, LDL receptor binding, dominant inheritance, three-dimensional structure, computer modeling, amino acid substitutions, lipoprotein metabolism
MeSH terms: Apolipoproteins E, Female, Heterozygote, Humans, Hyperlipoproteinemia Type III, Image Processing, Computer-Assisted, Isoelectric Focusing, Middle Aged, Molecular Conformation, Receptors, LDL, Point Mutation, Apolipoprotein E2

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Three-dimensional structure of the LDL receptor-binding domain of the human apolipoprotein E2 (Arg136 → Cys) variant

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