title: A P-type ATPase importer that discriminates between essential and toxic transition metals.
abstract: Transition metals, although being essential cofactors in many physiological processes, are toxic at elevated concentrations. Among the membrane-embedded transport proteins that maintain appropriate intracellular levels of transition metals are ATP-driven pumps belonging to the P-type ATPase superfamily. These metal transporters may be differentiated according to their substrate specificities, where the majority of pumps can extrude either silver and copper or zinc, cadmium, and lead. In the present report, we have established the substrate specificities of nine previously uncharacterized prokaryotic transition-metal P-type ATPases. We find that all of the newly identified exporters indeed fall into one of the two above-mentioned categories. In addition to these exporters, one importer, Pseudomonas aeruginosa Q9I147, was also identified. This protein, designated HmtA (heavy metal transporter A), exhibited a different substrate recognition profile from the exporters. In vivo metal susceptibility assays, intracellular metal measurements, and transport experiments all suggest that HmtA mediates the uptake of copper and zinc but not of silver, mercury, or cadmium. The substrate selectivity of this importer ensures the high-affinity uptake of essential metals, while avoiding intracellular contamination by their toxic counterparts.
authors.affiliation: Division of Chemistry and Chemical Engineering 114-96 and Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA. lewinson@caltech.edu
authors.forename: Oded
authors.initials: O
authors.lastname: Lewinson
authors.forename: Allen T
authors.initials: AT
authors.lastname: Lee
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Rees
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000201:enzymology; D016415:Sequence Alignment; D013997:Time Factors; D028561:Transition Elements / Q000378:metabolism / Q000633:toxicity*
chemical_list: D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D028561:Transition Elements; D000251:Adenosine Triphosphatases