一个携带铜的PIB型ATPase的晶体结构
Pontus Gourdon1, Xiang-Yu Liu, Tina Skjørringe
1Centre for Membrane Pumps in Cells and Disease-PUMPKIN, Danish National Research Foundation, Aarhus University, Department of Molecular Biology, Gustav Wieds Vej 10C, DK-8000 Aarhus C, Denmark.
Nature
|July 1, 2011
概括
重金属排毒依赖于P型ATPases类IB (PIB).重金属排毒依赖于P型ATPases类IB (PIB). 这项研究揭示了Legionella pneumophila CopA的无铜结构,详细说明了其铜运输途径,并帮助分析人类疾病.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 微生物学 微生物学
背景情况:
- 重金属稳态对于细胞生存和功能至关重要.
- 类IB (PIB) 的P型ATPases对于从细胞中挤出有毒重金属至关重要.
研究的目的:
- 为了确定一个PIB-ATPase的结构,特别是Legionella pneumophila CopA Cu(+) -ATPase,在无铜状态下.
- 阐明铜运输路径和PIB-ATPases的机制.
- 为了解与ATP7A和ATP7B相关的人类疾病提供结构基础.
主要方法:
- 在3.2 Å分辨率的X射线晶体学.
- 在Legionella pneumophila CopA Cu(+) -ATPase.的结构分析.
主要成果:
- 确定了L. pneumophila CopA的无铜结构.
- 确定了一条三阶段的铜运输路径,涉及保存的残留物.
- 一个具有双甘氨酸图案的 PIB 特定的跨膜螺旋体形成了一个假定的细胞内铜入口点.
- 提出了一种通过细胞外退出部位释放与ATPase合的铜的机制.
结论:
- 确定的结构为重金属挤出机制提供了洞察力.
- 这些发现为分析人类ATP7A和ATP7B突变提供了一个框架,这些突变与门克斯和威尔逊病有关.
- 这项研究促进了对金属酶结构和功能在解毒途径中的理解.
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