过氧体Pex1/Pex6 ATPase复合体与基质结合的结构
Maximilian Rüttermann1,2, Michelle Koci3, Pascal Lill1,2,3
1Institute for Medical Physics and Biophysics, University Münster, Münster, Germany.
Nature communications
|September 23, 2023
概括
这项研究揭示了Pex1/Pex6 AAA+ ATPase的结构,这对过氧体功能至关重要. 它揭示了这种复杂物如何转移基质,提供了对氧体疾病的见解.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 结构生物学 结构生物学
背景情况:
- 该AAA+ ATPase Pex1/Pex6对于过氧体生物发生和受体循环至关重要.
- 佩克斯1/佩克斯6中的突变导致与过氧体功能障碍相关的严重发育障碍.
- 佩克斯1/佩克斯6异质合体的详细机制仍然难以捉摸.
研究的目的:
- 阐明Pex1/Pex6函数的结构和机制基础.
- 要了解Pex1/Pex6是如何协调基质转位的.
- 为了深入了解背后的多氧体疾病的分子机制.
主要方法:
- 使用冷电子显微镜 (cryoEM) 确定了Saccharomyces cerevisiae Pex1/Pex6.1的结构.
- 一种内源性蛋白质基质被捕获在D2环的中央孔隙内.
- 结构分析的重点是Pex1/Pex6子域与基板之间的相互作用.
主要成果:
- 化EM结构揭示了带有被困基质的异构hexameric Pex1/Pex6复合体.
- 催化活跃的D2环通过孔-1循环与基质接触.
- 不活跃的D1环经历了形状变化,在D2中通过ATP水解来调节.
- 在Pex1/Pex6接口中发现了独特的机械力传播机制.
结论:
- 这项研究为Pex1/Pex6介导的基质转位提供了前所未有的结构洞察力.
- 它揭示了Pex1和Pex6在管理基质运动中的协调作用.
- 这些发现有助于理解氧体相关发育障碍的分子基础.
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