An arsenic metallochaperone for an arsenic detoxification pump

Abstract

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.