Crystal structure of a copper-transporting PIB-type ATPase
Crystal structure of a copper-transporting PIB-type ATPase
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DOI：
10.1038/nature10191
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发表时间：
2011-07-07
期刊：
影响因子：
64.8
通讯作者：
Nissen, Poul
中科院分区：
文献类型：
--
作者：
Gourdon, Pontus;Liu, Xiang-Yu;Nissen, Poul
重金属的体内平衡和解毒对细胞的生存能力至关重要。IB类（PIB）的P型ATP酶在这些过程中是必不可少的，积极地从细胞质中挤出重金属。在这里，我们提出的结构的PIB-ATP酶，嗜肺军团菌CopA Cu+-ATP酶，在无铜的形式，确定在3.2埃分辨率的X-射线晶体学。该结构表明一个三阶段的铜转运途径，涉及几个保守的残基。PIB特异性跨膜螺旋在双甘氨酸基序处扭结，显示出两亲性螺旋，该螺旋在细胞内界面处排列着推定的铜进入点。与Ca 2 +-ATP酶的比较表明，ATP酶偶联的铜释放机制从膜中的结合位点通过细胞外出口位点。该结构还提供了一个框架来分析与门克斯病和威尔逊病相关的人类ATP 7A和ATP 7 B蛋白中的错义突变。
Heavy-metal homeostasis and detoxification is crucial for cell viability. P-type ATPases of the class IB (PIB) are essential in these processes, actively extruding heavy metals from the cytoplasm of cells. Here we present the structure of a PIB-ATPase, a Legionella pneumophila CopA Cu+-ATPase, in a copper-free form, as determined by X-ray crystallography at 3.2 angstrom resolution. The structure indicates a three-stage copper transport pathway involving several conserved residues. A PIB-specific transmembrane helix kinks at a double-glycine motif displaying an amphipathic helix that lines a putative copper entry point at the intracellular interface. Comparisons to Ca2+-ATPase suggest an ATPase-coupled copper release mechanism from the binding sites in the membrane via an extracellular exit site. The structure also provides a framework to analyse missense mutations in the human ATP7A and ATP7B proteins associated with Menkes' and Wilson's diseases.