Hidden Aggregation Hot-Spots on Human Apolipoprotein E: A Structural Study
AbstractHuman 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
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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.
Tsiolaki PL, Katsafana AD, Baltoumas FA, Louros NN, Iconomidou VA. Hidden Aggregation Hot-Spots on Human Apolipoprotein E: A Structural Study. International Journal of Molecular Sciences. 2019; 20(9):2274.Chicago/Turabian Style
Tsiolaki, Paraskevi L.; Katsafana, Aikaterini D.; Baltoumas, Fotis A.; Louros, Nikolaos N.; Iconomidou, Vassiliki A. 2019. "Hidden Aggregation Hot-Spots on Human Apolipoprotein E: A Structural Study." Int. J. Mol. Sci. 20, no. 9: 2274.
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