The transport mechanism of bacterial Cu+-ATPases: distinct efflux rates adapted to different function.
The transport mechanism of bacterial Cu+-ATPases: distinct efflux rates adapted to different function.
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DOI：
10.1007/s10534-010-9404-3
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发表时间：
2011-06
期刊：
影响因子：
3.5
通讯作者：
Argueello, Jose M.
中科院分区：
文献类型：
--
作者：
Raimunda, Daniel;Gonzalez-Guerrero, Manuel;Leeber, Blaise W., III;Argueello, Jose M.
Cu2+-ATPase通过参与Cu2+解毒和CuProtein组装，在细菌的Cu2+动态平衡中起着关键作用。黄褐古球藻是P1B-1型ATPase亚家族中的一个模式蛋白，它的特性提供了这类转运蛋白的结构和机制细节。细胞质调节金属结合域(MBDS)和催化致动器、磷酸化和核苷酸结合域的原子分辨结构是可用的。这些结合了冷冻电子显微镜分析得到的整个蛋白质结构，使这些转运蛋白的初步建模成为可能。螺旋6、7和8上的不变残基形成两个跨膜金属结合位点(TM-MBSS)。它们以高亲和力在三角平面构型中结合了铜离子。细胞质中的铜伴侣CopZ将金属直接转移到TM-MBSS；然而，装载这两种TM-MBSS需要核苷酸与酶结合。与经典的P型ATPase转运机制一致，胞质铜离子占据这两个跨膜位点是酶磷酸化和随后转运到胞外或胞外环境的必要条件。最近的转运研究表明，所有的铜-三磷酸腺苷酶都能驱动细胞质中的铜离子外流，尽管其转运速率因其不同的生理作用而有很大的不同。典型的负责铜离子耐受性的铜离子外排泵，如大肠杆菌COPA，其周转率比参与铜蛋白组装(或替代功能)的泵高十倍。这解释了后者无法显著促进在高铜环境中生存所需的金属外流。
Cu+-ATPases play a key role in bacterial Cu+ homeostasis by participating in Cu+ detoxification and cuproprotein assembly. Characterization of Archaeoglobus fulgidus CopA, a model protein within the subfamily of P1B-1 type ATPases, has provided structural and mechanistic details on this group of transporters. Atomic resolution structures of cytoplasmic regulatory metal binding domains (MBDs) and catalytic actuator, phosphorylation, and nucleotide binding domains are available. These, in combination with whole protein structures resulting from cryo-electron microscopy analyses, have enabled the initial modeling of these transporters. Invariant residues in helixes 6, 7 and 8 form two transmembrane metal binding sites (TM-MBSs). These bind Cu+ with high affinity in a trigonal planar geometry. The cytoplasmic Cu+ chaperone CopZ transfers the metal directly to the TM-MBSs; however, loading both of the TM-MBSs requires binding of nucleotides to the enzyme. In agreement with the classical transport mechanism of P-type ATPases, occupancy of both transmembrane sites by cytoplasmic Cu+ is a requirement for enzyme phosphorylation and subsequent transport into the periplasmic or extracellular milieus. Recent transport studies have shown that all Cu+-ATPases drive cytoplasmic Cu+ efflux, albeit with quite different transport rates in tune with their various physiological roles. Archetypical Cu+-efflux pumps responsible for Cu+ tolerance, like the Escherichia coli CopA, have turnover rates ten times higher than those involved in cuproprotein assembly (or alternative functions). This explains the incapability of the latter group to significantly contribute to the metal efflux required for survival in high copper environments.
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DOI：
10.1073/pnas.0711446105
发表时间：
2008-04-22
影响因子：
11.1
作者：
Gonzalez-Guerrero, Manuel;Argueello, Jose M.
通讯作者：
Argueello, Jose M.
影响因子：
2.1
作者：
Frangipani, Emanuela;Haas, Dieter
通讯作者：
Haas, Dieter
影响因子：
4.8
作者：
Hatori, Yuta;Hirata, Ayami;Inesi, Giuseppe
通讯作者：
Inesi, Giuseppe
影响因子：
4.8
作者：
Fan, B;Rosen, BP
通讯作者：
Rosen, BP
影响因子：
4.8
作者：
Eisses, JF;Kaplan, JH
通讯作者：
Kaplan, JH