Why Is the C-terminus of Aβ(1-42) More Unfolded than That of Aβ(1-40)? Clues from Hydrophobic Interaction
Aβ(1-40) and Aβ(1-42) are the main forms of amyloid β (Aβ) peptides in the brain of Alzheimers patients; however, the latter possesses much stronger aggregation and deposition propensity than the former, which is partially attributed to the more unfolded C-terminus of Aβ(1-42) than that of Aβ(1-40). To explore the physical basis underlying the different dynamic behaviors of both Aβ peptides, parallel molecular dynamics (MD) simulations on Aβ(1-40) and Aβ(1-42) were performed to investigate their thermal unfolding processes. It is revealed that the addition of residues 41 and 42 in Aβ(1-42) disrupts the C-terminal hydrophobic core, which triggers the unraveling of the C-terminal helix of Aβ(1-42). This conclusion is supported by the MD simulation on the I41A mutant of Aβ(1-42), in which the C-terminal helix possesses relatively higher conformational stability than that of wild type Aβ(1-42) owing to the change in hydrophobic interaction patterns.
Liang Shen Hong-Fang Ji Hong-Yu Zhang
Shandong Provincial Research Center for Bioinformatic Engineering and Technique, Center for Advanced Study, Shandong University of Technology, Zibo 255049, Peoples Republic of China
国际会议
广州
英文
562-565
2008-11-01（万方平台首次上网日期，不代表论文的发表时间）