Lewinson, Oded and Lee, Allen T. and Rees, Douglas C. (2009) A P-type ATPase importer that discriminates between essential and toxic transition metals. Proceedings of the National Academy of Sciences of the United States of America, 106 (12). pp. 4677-4682. ISSN 0027-8424 http://resolver.caltech.edu/CaltechAUTHORS:20090624-100450865
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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.
|Additional Information:||© 2009 by the National Academy of Sciences. Freely available online through the PNAS open access option. Contributed by Douglas C. Rees, January 26, 2009 (received for review October 15, 2008). http://dx.doi.org/10.1073/pnas.0900666106 We thank Nathan Dalleska and the Environmental Analysis Center for assistance with the metal analyses. The work was supported in part by National Institutes of Health Grant GM045162, by the Howard Hughes Medical Institute, and by fellowships to O.L. from the Fulbright Foundation and the Jane Coffin Childs Memorial Fund for Medical Research. Author contributions: O.L. and D.C.R. designed research; O.L. and A.T.L. performed research; O.L., A.T.L., and D.C.R. analyzed data; and O.L. and D.C.R. wrote the paper. The authors declare no conflict of interest.|
|Subject Keywords:||membrane proteins; transition-metal homeostasis; heavy metal transporters; P-1B ATPases|
|Usage Policy:||No commercial reproduction, distribution, display or performance rights in this work are provided.|
|Deposited By:||Tony Diaz|
|Deposited On:||13 Aug 2009 15:08|
|Last Modified:||26 Dec 2012 11:03|
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