ArsD: an As(III) metallochaperone for the ArsAB As(III)-translocating ATPase |
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Authors: | Yung-Feng Lin Jianbo Yang Barry P Rosen |
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Institution: | (1) Department of Biochemistry and Molecular Biology, Wayne State University, School of Medicine, Detroit, MI 48201, USA;(2) Present address: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA |
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Abstract: | The toxic metalloid arsenic is widely disseminated in the environment and causes a variety of health and environment problems.
As an adaptation to arsenic-contaminated environments, organisms have developed resistance systems. Many ars operons contain only three genes, arsRBC. Five gene ars operons have two additional genes, arsD and arsA, and these two genes are usually adjacent to each other. ArsA from Escherichia coli plasmid R773 is an ATPase that is the catalytic subunit of the ArsAB As(III) extrusion pump. ArsD was recently identified
as an arsenic chaperone to the ArsAB pump, transferring the trivalent metalloids As(III) and Sb(III) to the ArsA subunit of
the pump. This increases the affinity of ArsA for As(III), resulting in increased rates if extrusion and resistance to environmentally
relevant concentrations of arsenite. ArsD is a homodimer with three vicinal cysteine pairs, Cys12–Cys13, Cys112–Cys113 and
Cys119–Cys120, in each subunit. Each vicinal pair binds one As(III) or Sb(III). ArsD mutants with alanines substituting for
Cys112, Cys113, Cys119 or Cys120, individually or in pairs or truncations lacking the vicinal pairs, retained ability to interact
with ArsA, to activate its ATPase activity. Cells expressing these mutants retained ArsD-enhanced As(III) efflux and resistance.
In contrast, mutants with substitutions of conserved Cys12, Cys13 or Cys18, individually or in pairs, were unable to activate
ArsA or to enhance the activity of the ArsAB pump. It is proposed that ArsD residues Cys12, Cys13 and Cys18, but not Cys112,
Cys113, Cys119 or Cys120, are required for delivery of As(III) to and activation of the ArsAB pump. |
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Keywords: | Arsenic Arsenite Antimony Resistance pump ArsD ArsA |
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