ArticleProceedings of the National Academy of Sciences of the United States of America2011
Topology of human apolipoprotein E3 uniquely regulates its diverse biological functions.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 156 papers.
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Who cites it
156 citing papers in PubMed, 274 citations in OpenAlex.
- Article
- Article
- Protective mutations associated with APOE in Alzheimer's disease.Molecular psychiatry · 2026Review
- Computational Selectivity Analysis of Aptamer toward Oxidized Low-Density Lipoprotein.ACS omega · 2026Article
- XL-MS and De Novo Protein Design Identified a Common Motif for TREM2 Binding.bioRxiv : the preprint server for biology · 2026Article
- Transcriptome Sequencing and Identification ofAnimals : an open access journal from MDPI · 2026Article
- Structural Change of ApoE-Lipid Nanoparticles Alters Receptor-Mediated Endocytosis and Induces Endosomal Disruption.Journal of the American Chemical Society · 2026Article
- Is there a role for apolipoprotein E in perinatal brain injury?Molecular and cellular pediatrics · 2026Review
- Article
- APOE Genotype Difference in the Biphasic Modulation of Amyloid-β Aggregation by Direct Binding and Lowering the Nucleation Barrier.Biomacromolecules · 2025Article
- The Christchurch point mutation in mouse APOE reduces Aβ-induced tau and α-synuclein pathologies.bioRxiv : the preprint server for biology · 2025Article
- TREM2-apoE3 interactions and Alzheimer's disease: Molecular and structural insights and effects of TREM2 R47H and apoE4 variants.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Molecular dynamics of select missense mutations of Apolipoprotein E and their implications in Hyperlipoproteinemia type III.Biochemistry and biophysics reports · 2025Article
- Article
- Metabolic Dysfunction-Associated Steatotic Liver Disease: From a Very Low-Density Lipoprotein Perspective.Biomolecules · 2025Review
- Increased cerebrospinal fluid and plasma apoE glycosylation is associated with reduced levels of Alzheimer's disease biomarkers.Alzheimer's research & therapy · 2025Article
- Conformational features of guinea pig apolipoprotein E offer insights into functioning of human apolipoprotein E.Archives of biochemistry and biophysics · 2025Article
- ApoE3 Christchurch and tau interaction as a protective mechanism against Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Article
- Discovery of an ApoE4-targeted small-molecule SirT1 enhancer for the treatment of Alzheimer's disease.Scientific reports · 2025Article
96 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Human apolipoprotein E (apoE) is one of the major determinants in lipid transport, playing a critical role in atherosclerosis and other diseases. Binding to lipid and heparan sulfate proteoglycans (HSPG) induces apoE to adopt active conformations for binding to low-density lipoprotein receptor (LDLR) family. ApoE also interacts with beta amyloid peptide, manifests critical isoform-specific effects on Alzheimer's disease. Despite the importance of apoE in these major human diseases, the fundamental questions of how apoE adjusts its structure upon binding to regulate its diverse functions remain unsolved. We report the NMR structure of apoE3, displaying a unique topology of three structural domains. The C-terminal domain presents a large exposed hydrophobic surface that likely initiates interactions with lipids, HSPG, and beta amyloid peptides. The unique topology precisely regulates apoE tertiary structure to permit only one possible conformational adaptation upon binding and provides a double security in preventing lipid-free and partially-lipidated apoE from premature binding to apoE receptors during receptor biogenesis. This topology further ensures the optimal receptor-binding activity by the fully lipidated apoE during lipoprotein transport in circulation and in the brain. These findings provide a structural framework for understanding the structural basis of the diverse functions of this important protein in human diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.