M35 oxidation induces Abeta40-like structural and dynamical changes in Abeta42.

M35 oxidation induces Abeta40-like structural and dynamical changes in Abeta42.
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M35 氧化诱导 Abeta42 中类似 Abeta40 的结构和动力学变化。

DOI:
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发表时间:
2008
影响因子:
15
通讯作者:
Chunyu Wang
Chunyu Wang
中科院分区:
化学1区
文献类型:
--
作者:
Yilin Yan;S. McCallum;Chunyu Wang

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氧化 Abeta 的单个 M35 残基会导致聚集延迟并降低毒性。为了了解这种效应的分子机制,我们研究了 M35 氧化的结构和动力学后果。我们发现 Abeta42 C 端残基的迁移率在 M35 氧化后大大增强。相反,中心疏水簇中的甲基变得不太灵活。综上所述,我们得出结论,Abeta42ox 经历了类似 Abeta40 的结构和动力学变化,这有助于减少其聚集和毒性。
Oxidizing a single M35 residue of Abeta leads to delayed aggregation and reduced toxicity. To understand the molecular mechanism of this effect, we examined the structural and dynamical consequences of M35 oxidation. We found the mobility of the C-terminal residues of Abeta42 is greatly enhanced upon M35 oxidation. In contrast, methyl groups in the central hydrophobic cluster become less flexible. Taken together, we conclude that Abeta42ox undergoes Abeta40-like structural and dynamical changes, which contribute to its reduced aggregation and toxicity.