Disruption of the zinc finger domain: a common target that underlies many of the effects of lead.
Disruption of the zinc finger domain: a common target that underlies many of the effects of lead.
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DOI：
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发表时间：
2000-12
期刊：
影响因子：
3.4
通讯作者：
N. Zawia;T. Crumpton;M. Brydie;G. R. Reddy;M. Razmiafshari
中科院分区：
文献类型：
--
作者：
N. Zawia;T. Crumpton;M. Brydie;G. R. Reddy;M. Razmiafshari
与铅等重金属接触相关的健康风险仍然是一个主要的公共卫生问题。锌指是蛋白质-核酸相互作用的主要结构基序，存在于最大的转录因子超家族中。锌（Zn）离子通过与半胱氨酸和组氨酸残基形成的键来协调这种指状结构。关于重金属对含有这种结构重复的蛋白质的影响的信息很少。我们在神经系统中的研究表明，含有这种图案的因素可能是潜在的目标，由铅扰动。我们已经观察到，金属，如铅干扰的Sp1和Egr-1的DNA结合特性，在体内和体外。铅也可以直接干扰重组人Sp1蛋白的DNA结合。最近，铅对锌指蛋白转录因子IIIA（TFIIIA）的DNA结合的影响已被证明。铅对Sp1的影响分析表明，其DNA结合的变化与其靶基因表达的变化是相称的。铅对Sp1，Egr-1和TFIIIA的作用表明，它也可以靶向含有锌指基序的其他细胞蛋白，并揭示了该蛋白质结构域作为铅诱导的蛋白质功能改变的潜在介质。因此，通过特异性靶向锌指蛋白（ZFP），铅能够通过其作用于酶、通道和受体中存在的共同位点产生多种反应。
The health risks associated with exposure to heavy metals such as lead (Pb) remain a major public health concern. The zinc finger is a major structural motif involved in protein-nucleic acid interactions and is present in the largest superfamily of transcription factors. Zinc (Zn) ions coordinate this finger-like structure through bonds created with cysteine and histidine residues. Little information exists on the effects of heavy metals on proteins that contain structural repeats of this kind. Studies by us in the nervous system have shown that factors containing such motifs could be potential targets for perturbation by Pb. We have observed that metals such as Pb interfered with the DNA-binding properties of Sp1 and Egr-1, both in vivo and in vitro. Pb could also directly interfere with the DNA-binding of a recombinant human Sp1 protein. More recently, the effects of Pb on the DNA-binding of the zinc finger protein transcription factor IIIA (TFIIIA) have been demonstrated. Analysis on the effects of Pb on Sp1 revealed that alterations in its DNA-binding were commensurate with changes in the expression of its target genes. The action of Pb on Sp1, Egr-1, and TFIIIA suggests that it can also target other cellular proteins that contain the zinc finger motif and reveals this protein domain as a potential mediator for Pb-induced alterations in protein function. Thus by specifically targeting zinc finger proteins (ZFP), Pb is able to produce multiple responses through its action on a common site that is present in enzymes, channels and receptors.