Structural characterization of heavy metal detoxification by a bacterial Atm1-family 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 anal. 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 crystallog. characterization of the dimeric Atm1/ABCB7/HMT1/ABCB6 ortholog from Novosphingobium aromaticivorans DSM 12444 (NaAtm1) at 2.4 Angstrom resoln. The functional characterization of NaAtm1 proved that NaAtm1 is a glutathione (GSH) transporting heavy metal resistance protein. The substrate bound structures elucidated that the amino and carbonyl groups of y-Glu are crit. for GSH binding, and the presence of the second oxidized GSH binding site hints how tetra GSH metal adduct ligands may bind the transporter. Detailed mapping of the binding interactions highlighted the articulated design of ABC exporters with the key ligand interactions 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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