Fine control of metal concentrations is necessary for cells to discern zinc from cobalt.
Fine control of metal concentrations is necessary for cells to discern zinc from cobalt.
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DOI：
10.1038/s41467-017-02085-z
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发表时间：
2017-12-01
影响因子：
16.6
通讯作者：
Robinson NJ
中科院分区：
文献类型：
--
作者：
Osman D;Foster AW;Chen J;Svedaite K;Steed JW;Lurie-Luke E;Huggins TG;Robinson NJ
细菌具有转录因子，其dna结合活性在与特定金属结合时发生改变，但金属结合在体外不具有特异性。本研究表明，细胞内缓冲金属浓度的严格调控是鼠伤寒沙门菌中Zur、ZntR、RcnR和FrmR金属特异性的先决条件。在细胞中，在非抑制性浓度升高时，Zur和ZntR仅对Zn（II）有反应，RcnR对钴有反应，FrmR对甲醛有反应。然而，在体外，所有这些传感器结合非同源金属，这改变了DNA结合。我们根据每个载子和金属化传感器的确定丰度、金属亲和力和DNA亲和力，对这些传感器对细胞内Co（II）和Zn（II）缓冲浓度的响应进行了建模。同源传感器被模拟为对其同源金属的最低浓度作出反应，这解释了特异性。然而，其他传感器的模拟反应浓度仅略高，而钴或锌（II）冲击触发的错误反应与这些预测相匹配。因此，完美的金属特异性被微调到一个狭窄的缓冲细胞内金属浓度范围。细菌具有转录因子，其dna结合活性在与特定金属结合时发生改变，但在体外与金属的结合不具有特异性。在这里，Osman等人表明，严格调节缓冲细胞内金属浓度是金属特异性的先决条件。
Bacteria possess transcription factors whose DNA-binding activity is altered upon binding to specific metals, but metal binding is not specific in vitro. Here we show that tight regulation of buffered intracellular metal concentrations is a prerequisite for metal specificity of Zur, ZntR, RcnR and FrmR in Salmonella Typhimurium. In cells, at non-inhibitory elevated concentrations, Zur and ZntR, only respond to Zn(II), RcnR to cobalt and FrmR to formaldehyde. However, in vitro all these sensors bind non-cognate metals, which alters DNA binding. We model the responses of these sensors to intracellular-buffered concentrations of Co(II) and Zn(II) based upon determined abundances, metal affinities and DNA affinities of each apo- and metalated sensor. The cognate sensors are modelled to respond at the lowest concentrations of their cognate metal, explaining specificity. However, other sensors are modelled to respond at concentrations only slightly higher, and cobalt or Zn(II) shock triggers mal-responses that match these predictions. Thus, perfect metal specificity is fine-tuned to a narrow range of buffered intracellular metal concentrations. Bacteria possess transcription factors whose DNA-binding activity is altered upon binding to specific metals, but the binding of metals is not specific in vitro. Here, Osman et al. show that tight regulation of buffered intracellular metal concentrations is a prerequisite for metal specificity.
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影响因子：
16.6
作者：
Chen TY;Santiago AG;Jung W;Krzemiński Ł;Yang F;Martell DJ;Helmann JD;Chen P
通讯作者：
Chen P
影响因子：
14.8
作者：
Foster AW;Pernil R;Patterson CJ;Scott AJP;Pålsson LO;Pal R;Cummins I;Chivers PT;Pohl E;Robinson NJ
通讯作者：
Robinson NJ
DOI：
10.1074/jbc.m111.338301
发表时间：
2012-04-06
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Foster AW;Patterson CJ;Pernil R;Hess CR;Robinson NJ
通讯作者：
Robinson NJ
大肠杆菌K-12的构造框架，单基因敲除突变体：Keio Collection。
影响因子：
9.9
作者：
通讯作者：
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DOI：
10.1038/nrmicro2836
发表时间：
2012-07-16
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
通讯作者：
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