Lin Yung-Feng, Walmsley Adrian R, Rosen Barry P
Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Proc Natl Acad Sci U S A. 2006 Oct 17;103(42):15617-22. doi: 10.1073/pnas.0603974103. Epub 2006 Oct 9.
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.
环境砷是一个全球性的健康问题，这使得我们必须了解类金属摄取和解毒的机制。细胞内的主要形式是剧毒的亚砷酸盐，它通过从细胞质中去除而被解毒。当亚砷酸盐扩散通过细胞质到达外排系统时，是什么阻止了它的毒性？尽管细胞内的铜由金属伴侣蛋白调节，但尚未发现参与赋予对其他金属抗性的伴侣蛋白。在本文中，我们报告了对一种砷伴侣蛋白ArsD的鉴定，它由大肠杆菌的arsRDABC操纵子编码。ArsD将三价类金属转移到ArsA，后者是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其ATP酶活性，并提高亚砷酸盐的外排速率。因此，细胞对环境浓度的砷具有抗性。这份关于砷伴侣蛋白的报告表明，细胞调节亚砷酸盐的细胞内浓度以防止毒性。
