The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Three-Dimensional Structure of the LDL Receptor-Binding Domain of Human Apolipoprotein E
Abstract
Human apolipoprotein E, a blood plasma protein, mediates the transport and uptake of cholesterol and lipid by way of its high affinity interaction with different cellular receptors, including the low-density lipoprotein (LDL) receptor. The three-dimensional structure of the LDL receptor-binding domain of apoE has been determined at 2.5 angstrom resolution by x-ray crystallography. The protein forms an unusually elongated (65 angstroms) four-helix bundle, with the helices apparently stabilized by a tightly packed hydrophobic core that includes leucine zipper-type interactions and by numerous salt bridges on the mostly charged surface. Basic amino acids important for LDL receptor binding are clustered into a surface patch on one long helix. This structure provides the basis for understanding the behavior of naturally occurring mutants that can lead to atherosclerosis.
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In the citing paper
“with apoE2 having reduced binding affinity for the low density lipoprotein (LDL) receptor [5]”
From Blocking the apoE/Aβ interaction ameliorates Aβ-related pathology in APOE ε2 and ε4 targeted replacement Alzheimer model mice (2014) · cites this paper as [5]
In the citing paper
“This notion may explain enhanced Aβ clearance in the setting of apoE2, which is defective in LDL receptor binding [4,5].”
From Blocking the apoE/Aβ interaction ameliorates Aβ-related pathology in APOE ε2 and ε4 targeted replacement Alzheimer model mice (2014) · cites this paper as [5]
In the citing paper
“X-ray crystallography studies showed that the N-terminal domain is folded into a four-helix bundle of amphipathic α-helices spanning residues 24-164 that are stabilized by hydrophobic interactions and salt bridges [15], [16], [17].”
From Biophysical Analysis of Apolipoprotein E3 Variants Linked with Development of Type III Hyperlipoproteinemia (2011) · cites this paper as [15]
In the citing paper
“The sevenamino acid insertion in apoE Leiden occurs in a loop that connectshelix 3 to helix 4 in the 4-helical bundle of the amino-terminal domain of apoE(25).”
From Preferential association of apolipoprotein E Leiden with very low density lipoproteins of human plasma. (1993) · cites this paper as [25]
In the citing paper
“X-ray crystallographic analysis of the lipid-free apoE amino-terminal domain (residues 1-191) showed a 4 helix bundle spanning residues 24 -164 that segregates the hydrophobic core of the four helices from the solvent (23).”
From Molecular Basis for Increased Risk for Late-onset Alzheimer Disease Due to the Naturally Occurring L28P Mutation in Apolipoprotein E4 (2014) · cites this paper as [23]
In the citing paper
“The first structural determination of the N-terminal domain of apoE3, reported in 1991, indicated that it is a unique four-α-helix bundle (Fig.2)9, 10).”
From Impact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features (2025) · cites this paper as [9]
In the citing paper
“Early studies have characterized the structure of nonlipidated ApoE revealing that the nonlipidated N-terminal half of ApoE adopts a compact four-helix bundle [53].”
From ApoE lipoproteins in the central nervous system under homeostasis and role in Alzheimer’s disease and related disorders (2026) · cites this paper as [53]
In the citing paper
“The N-terminal domain is folded into a four-helix bundle of amphipathic α-helices and contains the LDLR binding region (around residues 136–150 in helix 4) (20)”
From 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 (2008) · cites this paper as [20]
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Metadata
- Authors
- Wilson, C., Wardell, M. R., Weisgraber, K. H., Mahley, R. W., & Agard, D. A.
- Affiliations
- Howard Hughes Medical Institute (US)
- University of California, San Francisco (US)
- Venue
- Science
- Published
- 1991-06-28
- Volume
- 252
- Issue
- 5014
- Pages
- 1817-1822
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1994543234
- Cited by
- 678
- References
- 41
- Citations by year
- 2026: 11 · 2025: 14 · 2024: 11 · 2023: 18 · 2022: 10 · 2021: 11 · 2020: 9 · 2019: 13 · 2018: 12 · 2017: 15 · 2016: 15 · 2015: 9 · 2014: 24 · 2013: 13 · 2012: 19
- FWCI
- 9.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL-41633, P01HL041633)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Keywords
- apolipoprotein E, protein structure, four-helix bundle, hydrophobic core, leucine zipper, salt bridges, basic amino acid clusters, atherosclerosis, cholesterol transport, ligand-receptor interactions
- MeSH terms
- Amino Acid Sequence, Apolipoproteins E, Binding Sites, Computer Graphics, Humans, Models, Molecular, Molecular Sequence Data, Protein Conformation, Receptors, LDL, X-Ray Diffraction
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