Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Via Vivaldi 43, 81100 Caserta, Italy.
Metallomics. 2014 Jan;6(1):96-104. doi: 10.1039/c3mt00208j.
Given the similar chemical properties of zinc and cadmium, zinc finger domains have been often proposed as mediators of the toxic and carcinogenic effects exerted by this xenobiotic metal. The effects of zinc replacement by cadmium in different eukaryotic zinc fingers have been reported. In the present work, to evaluate the effects of such substitution in the prokaryotic zinc finger, we report a detailed study of its functional and structural consequences on the Ros DNA binding domain (Ros87). We show that this protein, which bears important structural differences with respect to the eukaryotic domains, appears to structurally tolerate the zinc to cadmium substitution and the presence of cadmium does not affect the DNA binding activity of the protein. Moreover, we show for the first time how zinc to cadmium replacement can also take place in a cellular context. Our findings both complement and extend previous results obtained for different eukaryotic zinc fingers, suggesting that metal substitution in zinc fingers may be of relevance to the toxicity and/or carcinogenicity mechanisms of this metal.
鉴于锌和镉具有相似的化学性质，锌指结构域常被认为是这种外源性金属发挥毒性和致癌作用的中介。已经有报道称，不同真核生物锌指中的锌被镉取代会产生影响。在本工作中，为了评估这种取代对原核锌指的影响，我们对其功能和结构后果进行了详细研究，以 Ros DNA 结合域（Ros87）为对象。我们表明，与真核结构域相比，该蛋白具有重要的结构差异，似乎在结构上能够耐受锌向镉的取代，而且镉的存在并不影响蛋白的 DNA 结合活性。此外，我们首次展示了锌向镉取代在细胞环境中是如何发生的。我们的发现既补充和扩展了以前在不同真核锌指上获得的结果，表明锌指中的金属取代可能与该金属的毒性和/或致癌机制有关。
