与神经退行性疾病相关的Cu/Zn-超氧化物脱酶的氧化变性
Moeno Yoshida1, Norifumi Muraki1, Michiko Tajiri2
1Department of Chemistry, Keio University, Yokohama, Japan.
Protein science : a publication of the Protein Society
|October 16, 2025
概括
在铜超氧化物脱酶 (SOD1) 中氧化Cys111触发了错误折叠,这是肌缩侧面硬化症 (ALS) 中的一个关键过程. 准这种氧化可能会阻止SOD1的发生.
科学领域:
- 生物化学 生物化学
- 神经科学是一个神经科学.
- 结构生物学 结构生物学
背景情况:
- 突变的铜-超氧化物脱酶 (SOD1) 的错误折叠是家族性肌缩侧面硬化症 (ALS) 的核心.
- 包括野生型形式在内的SOD1的氧化损伤与神经退行有关,但其对SOD1折叠的影响尚不清楚.
研究的目的:
- 为了研究氧化对SOD1结构和折叠的影响.
- 确定特定的氧化位点及其对SOD1稳定性的影响.
主要方法:
- 对apo-SOD1暴露于过氧化.
- 硫醇组的量化和质谱学.
- 分子动力学模拟和循环二极化谱学.
主要成果:
- 将Cys111氧化为硫酸会破坏SOD1二元接口,从而促进单体化.
- 单化促进了Cys6的氧化,导致结构破坏和醇损失.
- SOD1 变性因结合功能受损而加剧,这在 ALS 突变和缺乏症中很常见.
结论:
- Cys111氧化是SOD1病理错折的关键早期步骤.
- 调节Cys111氧化可能是与氧化应激和SOD1功能障碍相关的神经退行性疾病的治疗策略.
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