Department of Chemistry, Indian Institute of Technology Kharagpur, India.
Sister Nivedita University, New Town, India.
FEBS Lett. 2023 Apr;597(7):1041-1051. doi: 10.1002/1873-3468.14583. Epub 2023 Feb 2.
Of the proteinaceous β-sheet-rich amyloid fibrillar structures, the Aβ peptide, a component of the full-length Aβ involved in Alzheimer's disease, has similar toxicity to the parent peptide. In this study, the effects of homocysteine thiolactone (HCTL) and hydrogen peroxide (H O ) on the conformation and fibrillation propensity of the Aβ peptide were investigated. Both HCTL and H O induced amino acid modifications along with alteration in aggregation propensity. Methionine (Met)-35 was oxidized by H O and aggregation was attenuated following the increased hydrophilicity of the peptide due to sulfoxide/sulfone formation. The HCTL-modified lysine (Lys-28) residue destabilizes the structure of the peptide, which leads to fibrillation. Our studies provide important information regarding the relationship between amino acid modifications and the amyloid fibrillation process.
在富含蛋白质β-折叠的淀粉样纤维状结构中，Aβ 肽是全长 Aβ 的一个组成部分，与阿尔茨海默病有关，其毒性与母体肽相似。在这项研究中，研究了同型半胱氨酸硫内酯 (HCTL) 和过氧化氢 (H2O2) 对 Aβ 肽构象和纤维化倾向的影响。HCTL 和 H2O2 均诱导氨基酸修饰，并改变聚集倾向。H2O 氧化蛋氨酸 (Met)-35，由于亚砜/砜的形成增加了肽的亲水性，从而减弱了聚集。HCTL 修饰的赖氨酸 (Lys-28) 残基使肽的结构不稳定，导致纤维化。我们的研究提供了关于氨基酸修饰与淀粉样纤维形成过程之间关系的重要信息。
