Topic: Brain proteins, microglia and lab models
Interaction of the amino- and carboxyl-terminal domains in apolipoprotein (apo) E, referred to as domain interaction, is predicted to be more pronounced in apoE4 than in apoE3 and to underlie the association of apoE4 with Alzheimer and cardiovascular diseases. However, direct physical proof for the domain interaction concept is lacking. To address this issue, fluorescence resonance energy transfer and electron paramagnetic resonance spectroscopy were used to probe the spatial proximity of the two domains of apoE. Both methods demonstrated that the two domains are closer in both lipid-free and phospholipid-bound apoE4 than in apoE3 as a result of domain interaction. In addition, as shown by electron paramagnetic resonance, the domains of apoE4 move apart to resemble more closely the distance in apoE3 when the isoforms are bound to triglyceride-rich emulsion particles. These results demonstrate that domain interaction is a structural property of apoE4 and that apoE adopts different conformations when complexed to different lipids.
Key findings
- Both methods demonstrated that the two domains are closer in both lipid-free and phospholipid-bound apoE4 than in apoE3 as a result of domain interaction.
- These results demonstrate that domain interaction is a structural property of apoE4 and that apoE adopts different conformations when complexed to different lipids.
Why it matters
Using spectroscopy methods, this laboratory study found that the two domains of apolipoprotein E4 are closer together than in apolipoprotein E3, supporting the idea of domain interaction. This is basic structural research and does not show any treatment or prevention for Alzheimer disease.
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Study details
- Evidence strengthLow
How this study scored 42/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Journal of biological chemistry) |
| Journal's citation record | 4 / 4 | Journal of Biological Chemistry: journal h-index 780 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2005 — older than 20 years, still counted |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 88 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 3.8 citations a year over 23 year(s) since 2005 |
| Impact for its field and year | 3 / 6 | Cited 3.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 1 / 4 | Cited 10 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Karl Heinrich Weisgraber: h-index 96 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California, San Francisco: institution h-index 1,915 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 16076841) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 42 / 100 | — |
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Read the original
Full text: free to read — Unpaywall lists this copy as free to read: the link above (checked 10 Oct 2026).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Hatters, D. M., Budamagunta, M. S., Voss, J. C., & Weisgraber, K. H. (2005). Modulation of apolipoprotein E structure by domain interaction: differences in lipid-bound and lipid-free forms. The Journal of biological chemistry. https://doi.org/10.1074/jbc.m506044200
Vancouver
Hatters DM, Budamagunta MS, Voss JC, Weisgraber KH. Modulation of apolipoprotein E structure by domain interaction: differences in lipid-bound and lipid-free forms. The Journal of biological chemistry. 2005. doi:10.1074/jbc.m506044200. PMID: 16076841.
BibTeX
@article{hatters2005-16076841,
author = {Hatters, D. M. and Budamagunta, M. S. and Voss, J. C. and Weisgraber, K. H.},
title = {{Modulation of apolipoprotein E structure by domain interaction: differences in lipid-bound and lipid-free forms}},
journal = {The Journal of biological chemistry},
year = {2005},
doi = {10.1074/jbc.m506044200},
pmid = {16076841},
url = {https://doi.org/10.1074/jbc.m506044200}
}
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