Structural and functional characterization of a heavy metal detoxifying ABC transporter

Abstract

The superfamily of ATP Binding Cassette (ABC) transporters includes importers and exporters that translocate a wide variety of substrates across the cell membrane. Although significant progress has been achieved in the structural analysis of ABC exporters, much less is known about how ABC exporters selectively recognize varying substrates, and couple its binding to ATP hydrolysis. We have addressed these questions by the crystallographic and functional characterization of a dimeric Atm1/ABCB7/HMT1/ABCB6 bacterial ortholog. Glutathione and it's derivatives are demonstrated to serve as substrates. In vivo, this transporter confers resistance to silver and mercury toxicity to E. coli, implicating a physiological role in cellular detoxification processes. The 2.4 Angstrom resolution structure allowed detailed mapping of the binding interactions highlighting the articulated design of ABC exporters. The key ligand interactions are positioned at the boundaries between structurally conserved elements, which links ligand binding to the conformational changes underlying ATPase-coupled substrate translocation.

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