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|
| Type |
Poster Presentation |
| Area |
Physical Chemistry |
| Room No. |
Event Hall |
| Time |
4월 20일 (금요일) 11:00~12:30 |
| Code |
PHYS.P-212 |
| Subject |
Elucidating the molecular origin of the stronger aggregation propensity of Aβ42 than Aβ40 |
| Authors |
Yuxi Lin, Sihyun Ham*
Department of Chemistry, Sookmyung Women's University, Korea
|
| Abstract |
The self-assembly of the amyloid-β (Aβ) peptides is strongly related to the pathogenesis of Alzheimer’s disease. Among Aβ peptide alloforms, amyloid-β1-40 (Aβ40) and amyloid-β1-42 (Aβ42) are the most abundant ones in the human body. Although Aβ42 differs only by the additional I41A42 residues in the C-terminus, it exhibits a greater tendency to aggregate and much higher toxicity to neurons than Aβ40. Here, we investigated the molecular factors that influence the aggregation potential of Aβ42 and Aβ40, based on molecular dynamics simulations combined with solvation thermodynamic analyses. Although the two variants display structurally similar topologies, a slightly enhanced β-sheet forming tendency is observed in the C-terminal region of Aβ42 as compared to Aβ40. The thermodynamic decomposition analysis indicates that C-terminal region substantially increases the solvation free energy of Aβ42, which can be rationalized by the further dehydration of this region due to its enhanced formation of β-structure. Together with two additional hydrophobic residues (I41A42), this leads to the higher solvation free energy of Aβ42, implying a larger water-mediated attraction between Aβ42 monomers for the self-assembly. Our results provide structural and thermodynamic understanding on the role of the C-terminal region in increasing the aggregation propensity of Aβ42 relative to Aβ40 in aqueous solution. |
| E-mail |
Yuxi.Lin@hotmail.com |
|
121st General Meeting of the KCS