An arsenic metallochaperone for an arsenic detoxification pump
An arsenic metallochaperone for an arsenic detoxification pump
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DOI：
10.1073/pnas.0603974103
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发表时间：
2006-10-17
影响因子：
11.1
通讯作者：
Rosen, Barry P.
中科院分区：
文献类型：
--
作者：
Lin, Yung-Feng;Walmsley, Adrian R.;Rosen, Barry P.
环境砷是一个全球性的健康问题，使我们必须了解类金属的吸收和解毒机制。主要的细胞内形式是高度恶臭的亚砷酸盐，通过从细胞质中去除而解毒。当亚砷酸盐通过细胞质扩散到外排系统时，是什么阻止了它的毒性？虽然细胞内铜是由金属分子伴侣调节的，但还没有发现参与赋予对其他金属的抗性的分子伴侣。在这篇文章中，我们报告鉴定的砷伴侣，ArsD，编码的arsRDABC操纵子的大肠杆菌。ArsD将三价类金属转移到ArsA，作为As（III）/Sb（III）外排泵的催化亚基。与ArsD的相互作用增加了ArsA对亚砷酸盐的亲和力，从而在较低浓度的亚砷酸盐下增加了其ATP酶活性，并提高了亚砷酸盐的挤出速率。因此，细胞对环境中的砷浓度具有抵抗力。砷分子伴侣的这份报告表明，细胞调节细胞内的亚砷酸盐浓度，以防止毒性。
Environmental arsenic is a world-wide health issue, making it imperative for us to understand mechanisms of metalloid uptake and detoxification. The predominant intracellular form is the highly mephitic arsenite, which is detoxified by removal from cytosol. What prevents arsenite toxicity as it diffuses through cytosol to efflux systems? Although intracellular copper is regulated by metallochaperones, no chaperones involved in conferring resistance to other metals have been identified. In this article, we report identification of an arsenic chaperone, ArsD, encoded by the arsRDABC operon of Escherichia coli. ArsD transfers trivalent metalloids to ArsA, the catalytic subunit of an As(III)/Sb(III) efflux pump. Interaction with ArsD increases the affinity of ArsA for arsenite, thus increasing its ATPase activity at lower concentrations of arsenite and enhancing the rate of arsenite extrusion. Cells are consequently resistant to environmental concentrations of arsenic. This report of an arsenic chaperone suggests that cells regulate the intracellular concentration of arsenite to prevent toxicity.