Kinetic Mechanism of Amyloid-β-(16–22) Peptide Fibrillation,The Journal of Physical Chemistry Letters

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Kinetic Mechanism of Amyloid-β-(16–22) Peptide Fibrillation
The Journal of Physical Chemistry Letters ( IF 4.8 ) Pub Date : 2022-06-24 , DOI: 10.1021/acs.jpclett.2c01065
Moe Yamazaki ₁ , Keisuke Ikeda ₁ , Tomoshi Kameda ₂ , Hiroyuki Nakao ₁ , Minoru Nakano ₁

Affiliation

The kinetic mechanism of amyloid fibril formation by a peptide fragment containing seven residues of the amyloid-β protein Aβ-(16–22) was investigated. We found that the N- and C-terminal unprotected Aβ-(16–22), containing no aggregation nuclei, showed rapid fibrillation within seconds to minutes in a neutral aqueous buffer solution. The fibrillation kinetics were well described by the nucleation–elongation model, suggesting that primary nucleation was the rate-limiting step. On the basis of both experimental and theoretical analyses, the aggregated nucleus was estimated to be composed of 6–7 peptide molecules, wherein the two β-sheets were associated with their hydrophobic surfaces. Thin fibers with widths of 10–20 nm were formed, which increased their length and thickness, attaining a width of >20 nm over several tens of minutes, probably owing to the lateral association of the fibers. Electrostatic and hydrophobic interactions play important roles in aggregation. These results provide a basis for understanding the fibrillation of short peptides.

中文翻译：

淀粉样蛋白-β-（16-22）肽纤颤的动力学机制

研究了含有淀粉样蛋白-β 蛋白 Aβ-(16-22) 的七个残基的肽片段形成淀粉样蛋白原纤维的动力学机制。我们发现 N 端和 C 端未受保护的 Aβ-(16-22) 不含聚集核，在中性水性缓冲溶液中在几秒到几分钟内显示出快速原纤维化。成核-伸长模型很好地描述了原纤化动力学，表明初级成核是限速步骤。在实验和理论分析的基础上，估计聚集核由 6-7 个肽分子组成，其中两个 β-折叠与其疏水表面相关。形成宽度为 10-20 nm 的细纤维，这增加了它们的长度和厚度，在几十分钟内达到 >20 nm 的宽度，可能是由于纤维的横向结合。静电和疏水相互作用在聚集中起重要作用。这些结果为理解短肽的原纤维化提供了基础。

更新日期：2022-06-24

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