ArticleBiochemistry2008
Role of the N- and C-terminal domains in binding of apolipoprotein E isoforms to heparan sulfate and dermatan sulfate: a surface plasmon resonance study.
Article in Biochemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Regulation of autophagy, lipid metabolism, and neurodegenerative pathology by heparan sulfate proteoglycans.Frontiers in genetics · 2022Pooled it
- Age-related macular degeneration and cerebral amyloid angiopathy have similar pathologies from cholesterol-APOE-amyloid-β-complement mediated inflammation.Progress in retinal and eye research · 2026Review
- APOB to estimated APOB ratio for screening for the APOE2 genotype.medRxiv : the preprint server for health sciences · 2026Article
- Heparan sulphate and neural development: dissecting the roles of astrocyte-expressed heparan sulphate.Biochemical Society transactions · 2025Review
- Review
- A manifesto for Alzheimer's disease drug discovery in the era of disease-modifying therapies.Molecular neurodegeneration · 2025Review
- ApoE3 R136S binds to Tau and blocks its propagation, suppressing neurodegeneration in mice with Alzheimer's disease.Neuron · 2025Article
- Recruitment of apolipoprotein E facilitates Herpes simplex virus 1 attachment and release.Npj viruses · 2025Article
- Multi-functional role of apolipoprotein E in neurodegenerative diseases.Frontiers in aging neuroscience · 2025Review
- Beyond amyloid and tau: rethinking Alzheimer's disease through less explored avenues.Open biology · 2024Review
- Probing Protein Structural Changes in Alzheimer's Disease via Quantitative Cross-linking Mass Spectrometry.Analytical chemistry · 2024Article
- Vascular Heparan Sulfate and Amyloid-β in Alzheimer's Disease Patients.International journal of molecular sciences · 2024Article
- APOE Christchurch-mimetic therapeutic antibody reduces APOE-mediated toxicity and tau phosphorylation.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Cell type-specific roles of APOE4 in Alzheimer disease.Nature reviews. Neuroscience · 2024Review
- The APOE-R136S mutation protects against APOE4-driven Tau pathology, neurodegeneration and neuroinflammation.Nature neuroscience · 2023Article
- Apolipoprotein E Recognizes Alzheimer's Disease Associated 3-O Sulfation of Heparan Sulfate.Angewandte Chemie (International ed. in English) · 2023Article
- Heparan sulfate proteoglycan in Alzheimer's disease: aberrant expression and functions in molecular pathways related to amyloid-β metabolism.American journal of physiology. Cell physiology · 2023Review
- ApoE in Alzheimer's disease: pathophysiology and therapeutic strategies.Molecular neurodegeneration · 2022Review
- APOE in the bullseye of neurodegenerative diseases: impact of the APOE genotype in Alzheimer's disease pathology and brain diseases.Molecular neurodegeneration · 2022Review
- Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.Nature neuroscience · 2022Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
The ability of apolipoprotein E (apoE) to bind to cell-surface glycosaminoglycans (GAGs) is important for lipoprotein remnant catabolism. Using surface plasmon resonance, we previously showed that the binding of apoE to heparin is a two-step process; the initial binding involves fast electrostatic interaction, followed by a slower hydrophobic interaction. Here we examined the contributions of the N- and C-terminal domains to each step of the binding of apoE isoforms to heparan sulfate (HS) and dermatan sulfate (DS). ApoE3 bound to less sulfated HS and DS with a decreased favorable free energy of binding in the first step compared to heparin, indicating that the degree of sulfation has a major effect on the electrostatic interaction of GAGs with apoE. Mutation of a key Lys residue in the N-terminal heparin binding site of apoE significantly affected this electrostatic interaction. Progressive truncation of the C-terminal alpha-helical regions which favors the monomeric form of apoE3 greatly weakened the ability of apoE3 to bind to HS, with a much reduced favorable free energy of binding of the first step, suggesting that the C-terminal domain contributes to the GAG binding of apoE by the oligomerization effect. In agreement with this, dimerization of the apoE3 N-terminal fragment via disulfide linkage restored the electrostatic interaction of apoE with HS. Significantly, apoE4 exhibited much stronger binding to HS and DS than apoE2 or apoE3 in both lipid-free and lipidated states, perhaps resulting from enhanced electrostatic interaction through the N-terminal domain. This isoform difference in GAG binding of apoE may be physiologically significant such as in the retention of apoE-containing lipoproteins in the arterial wall.
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Registered trials
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