ArticleBiochemistry2014
Influence of domain stability on the properties of human apolipoprotein E3 and E4 and mouse apolipoprotein E.
Article in Biochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Human Apolipoprotein E ε4 Allele Modulates Energy Substrate Availability, Seizure Burden, Mortality and Hippocampal Injury, Cell Death, and Inflammation after Neonatal Hypoxic-Ischemic Brain Injury.Developmental neuroscience · 2026Article
- Surface Plasmon Resonance Based Binding Characterization for Screening RNA-Loaded Lipid Nanoparticles (LNPs): Exploring Species Cross-Reactivity in LNP-Apolipoprotein E Interactions.Molecular pharmaceutics · 2025Article
- Review
- APOE Christchurch enhances a disease-associated microglial response to plaque but suppresses response to tau pathology.Molecular neurodegeneration · 2025Article
- Modeling sporadic Alzheimer's disease in mice by combining Apolipoprotein E4 risk gene with environmental risk factors.Frontiers in aging neuroscience · 2024Article
- Inhibition of ACAT as a Therapeutic Target for Alzheimer's Disease Is Independent of ApoE4 Lipidation.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- ApoE isoform-specific differences in behavior and cognition associated with subchronic MPTP exposure.Learning & memory (Cold Spring Harbor, N.Y.) · 2020Article
- Sex-dependent effect ofDisease models & mechanisms · 2020Review
- Alzheimer's disease pathology in APOE transgenic mouse models: The Who, What, When, Where, Why, and How.Neurobiology of disease · 2020Review
- The Genetic Variability ofGenes · 2019Review
- Molecular Mechanisms of the R61T Mutation in Apolipoprotein E4: A Dynamic Rescue.Biophysical journal · 2017Article
- Peptide-Level Interactions between Proteins and Small-Molecule Drug Candidates by Two Hydrogen-Deuterium Exchange MS-Based Methods: The Example of Apolipoprotein E3.Analytical chemistry · 2017Article
- A mechanism for lipid binding to apoE and the role of intrinsically disordered regions coupled to domain-domain interactions.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Helical structure, stability, and dynamics in human apolipoprotein E3 and E4 by hydrogen exchange and mass spectrometry.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Swapping the N- and C-terminal domains of human apolipoprotein E3 and AI reveals insights into their structure/activity relationship.PloS one · 2017Article
- APOE genotype and stress response - a mini review.Lipids in health and disease · 2016Review
- Amyloid-Forming Properties of Human Apolipoproteins: Sequence Analyses and Structural Insights.Advances in experimental medicine and biology · 2015Review
- Fluorescence study of domain structure and lipid interaction of human apolipoproteins E3 and E4.Biochimica et biophysica acta · 2014Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
The human apolipoprotein (apo) E4 isoform, which differs from wild-type apoE3 by the single amino acid substitution C112R, is associated with elevated risk of cardiovascular and Alzheimer’s diseases, but the molecular basis for this variation between isoforms is not understood. Human apoE is a two-domain protein comprising an N-terminal helix bundle and a separately folded C-terminal region. Here, we examine the concept that the ability of the protein to bind to lipid surfaces is influenced by the stability (or readiness to unfold) of these domains. The lipid-free structures and abilities to bind to lipid and lipoprotein particles of a series of human and mouse apoE variants with varying domain stabilities and domain–domain interactions are compared. As assessed by urea denaturation, the two domains are more unstable in apoE4 than in apoE3. To distinguish the contributions of the destabilization of each domain to the greater lipid-binding ability of apoE4, the properties of the apoE4 R61T and E255A variants, which have the same helix bundle stabilities but altered C-terminal domain stabilities, are compared. In these cases, the effects on lipid-binding properties are relatively minor, indicating that the destabilization of the helix bundle domain is primarily responsible for the enhanced lipid-binding ability of apoE4. Unlike human apoE, mouse apoE behaves essentially as a single domain, and its lipid-binding characteristics are more similar to those of apoE4. Together, the results show that the overall stability of the entire apoE molecule exerts a major influence on its lipid- and lipoprotein-binding properties.
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