The residue lysine 28 (K28) is known to form an important salt bridge that stabilizes the Aβ amyloid structure, and acetylation of lysine 28 (K28Ac) slows the Aβ42 fibrillization rate but does not affect fibril morphology. On the other hand, acetylation of lysine 16 (K16Ac) residue greatly diminishes the fibrillization property of Aβ42 peptide and also affects its toxicity. This is due to the fact that lysine 16 acetylated amyloid beta peptide forms amorphous aggregates instead of amyloid fibrils. This is likely a result of increased hydrophobicity of the K16-A21 region due to K16 acetylation, as confirmed by molecular dynamic simulation studies. The calculated results show that the hydrophobic patches of aggregates from acetylated peptides were different when compared to wild-type (WT) peptide. K16Ac and double acetylated (KKAc) peptide aggregates show significantly higher cytotoxicity compared to the WT or K28Ac peptide aggregates alone. However, the heterogeneous mixture of WT and acetylated Aβ42 peptide aggregates exhibited higher free radical formation as well as cytotoxicity, suggesting dynamic interactions between different species could be a critical contributor to Aβ pathology.

中文翻译：

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Aβ42 在赖氨酸 16 处的乙酰化会破坏淀粉样蛋白的形成。

已知残基赖氨酸 28 (K28) 会形成重要的盐桥，稳定 Aβ 淀粉样蛋白结构，赖氨酸 28 (K28Ac) 的乙酰化会减慢 Aβ42 原纤维化速率，但不影响原纤维形态。另一方面，赖氨酸 16 (K16Ac) 残基的乙酰化大大降低了 Aβ42 肽的纤维化特性，并影响其毒性。这是因为赖氨酸 16 乙酰化淀粉样β肽形成无定形聚集体而不是淀粉样原纤维。分子动力学模拟研究证实，这可能是由于 K16 乙酰化而导致 K16-A21 区域疏水性增加的结果。计算结果表明，与野生型 (WT) 肽相比，乙酰化肽聚集体的疏水斑块不同。与单独的 WT 或 K28Ac 肽聚集体相比，K16Ac 和双乙酰化 (KKAc) 肽聚集体显示出显着更高的细胞毒性。然而，WT 和乙酰化 Aβ42 肽聚集体的异质混合物表现出更高的自由基形成和细胞毒性，表明不同物种之间的动态相互作用可能是 Aβ 病理学的关键因素。