Next Article in Journal
Sonic Hedgehog Signaling Is Required for Cyp26 Expression during Embryonic Development
Next Article in Special Issue
Accumulation of Innate Amyloid Beta Peptide in Glioblastoma Tumors
Previous Article in Journal
Using Thermography to Confirm Genotypic Variation for Drought Response in Maize
Previous Article in Special Issue
Prediction of Bioactive Peptides from Chlorella sorokiniana Proteins Using Proteomic Techniques in Combination with Bioinformatics Analyses
Article Menu
Issue 9 (May-1) cover image

Export Article

Open AccessArticle

Hidden Aggregation Hot-Spots on Human Apolipoprotein E: A Structural Study

Section of Cell Biology and Biophysics, Department of Biology, National and Kapodistrian University of Athens, Panepistimiopolis, Athens 15701, Greece
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(9), 2274; https://doi.org/10.3390/ijms20092274
Received: 10 April 2019 / Revised: 3 May 2019 / Accepted: 6 May 2019 / Published: 8 May 2019
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
  |  
PDF [1690 KB, uploaded 8 May 2019]
  |  

Abstract

Human apolipoprotein E (apoE) is a major component of lipoprotein particles, and under physiological conditions, is involved in plasma cholesterol transport. Human apolipoprotein E found in three isoforms (E2; E3; E4) is a member of a family of apolipoproteins that under pathological conditions are detected in extracellular amyloid depositions in several amyloidoses. Interestingly, the lipid-free apoE form has been shown to be co-localized with the amyloidogenic Aβ peptide in amyloid plaques in Alzheimer’s disease, whereas in particular, the apoE4 isoform is a crucial risk factor for late-onset Alzheimer’s disease. Evidence at the experimental level proves that apoE self-assembles into amyloid fibrilsin vitro, although the misfolding mechanism has not been clarified yet. Here, we explored the mechanistic insights of apoE misfolding by testing short apoE stretches predicted as amyloidogenic determinants by AMYLPRED, and we computationally investigated the dynamics of apoE and an apoE–Αβ complex. Our in vitro biophysical results prove that apoE peptide–analogues may act as the driving force needed to trigger apoE aggregation and are supported by the computational apoE outcome. Additional computational work concerning the apoE–Αβ complex also designates apoE amyloidogenic regions as important binding sites for oligomeric Αβ; taking an important step forward in the field of Alzheimer’s anti-aggregation drug development. View Full-Text
Keywords: apolipoprotein E; amyloid fibrils; Alzheimer’s disease; Αβ oligomer apolipoprotein E; amyloid fibrils; Alzheimer’s disease; Αβ oligomer
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Tsiolaki, P.L.; Katsafana, A.D.; Baltoumas, F.A.; Louros, N.N.; Iconomidou, V.A. Hidden Aggregation Hot-Spots on Human Apolipoprotein E: A Structural Study. Int. J. Mol. Sci. 2019, 20, 2274.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top