Apolipoprotein E isoform‐specific binding to the low‐density lipoprotein receptor
Open accessAbstract
Apolipoprotein E (apoE) is a ligand for members of the low-density lipoprotein receptor (LDLR) family and functions in plasma cholesterol homeostasis. A fluorescence-based assay has been employed in molecular studies of receptor-ligand interactions. Competition experiments revealed isoform-specific differences in binding of lipid-associated apoE N terminal (NT) domain to a recombinant soluble LDLR (sLDLR). In a similar manner, lipid--associated-but not lipid-free--full-length apoE3 showed binding activity to sLDLR. The molecular chaperone, receptor-associated protein, inhibited apoE3-NT-phospholipid complex binding to sLDLR. Kinetic studies of apoE3-NT-phospholipid complex interaction with sLDLR revealed time-dependent effects of apoE-NT isoform binding to sLDLR. The results reveal a discerning method for study of the molecular basis of ligand interactions that likely influence receptor function in maintenance of whole body cholesterol homeostasis.
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APOE2 exhibits a lower LDLR binding capacity than APOE4.
“Biochemical studies have also identified isoform‐specific differences in LDLR binding, with APOE2 exhibiting a lower binding capacity than APOE4 does.”
From Deletion of neuronal <i>Idol</i> ameliorates Alzheimer's disease–related pathologies via APOE receptors (2025) · cites this paper as [67]
Lipidated ApoE2 exhibits reduced binding to LDLR compared to ApoE3/E4.
“One of the most striking ApoE isoform-specific biochemical features is that ApoE2 exhibits defective binding to low density lipoprotein receptor (LDLR), based on ligand competition assays19,20.”
From Decreased lipidated ApoE‐receptor interactions confer protection against pathogenicity of ApoE and its lipid cargoes in lysosomes (2025) · cites this paper as [20]
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- Authors
- Yamamoto, T., Choi, H. W., & Ryan, R. O.
- Corresponding author
- Ryan, Robert O.
- ORCID
- Ryan, Robert O.
- Venue
- Analytical Biochemistry
- Publisher
- Elsevier BV
- Published
- 2008-01
- Volume
- 372
- Issue
- 2
- Pages
- 222-226
- ISSN
- 0003-2697 (ISSN-L)
- PMC
- PMC2174959
- OpenAlex
- W2053525596
- Cited by
- 59
- References
- 3
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 7 · 2023: 4 · 2022: 5 · 2021: 8 · 2020: 3 · 2019: 1 · 2018: 5 · 2017: 3 · 2016: 1 · 2015: 2 · 2014: 5 · 2013: 1 · 2012: 3
- FWCI
- 1.00
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Analytical Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL 64159, R37HL064159, R01HL064159)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- apolipoprotein E, apolipoprotein E isoforms, LDL receptor, ligand-receptor interactions, phospholipid complex, receptor-associated protein, cholesterol homeostasis, binding kinetics, competitive binding assay
- MeSH terms
- Apolipoproteins E, Cholesterol, Dimyristoylphosphatidylcholine, Homeostasis, Humans, Phospholipids, Protein Binding, Receptors, LDL, Recombinant Proteins, Substrate Specificity, Apolipoprotein A-I, Protein Isoforms, Apolipoprotein E3
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