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Prepublished online as a Blood First Edition Paper on January 9, 2003; DOI 10.1182/blood-2002-07-2108. This Article Full Text Full Text (PDF) Supplemental Data Set All Versions of this Article: 2002-07-2108v1 101/9/3699    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lam-Yuk-Tseung, S. Articles by Gros, P. Search for Related Content PubMed PubMed Citation Articles by Lam-Yuk-Tseung, S. Articles by Gros, P. Related Collections Phagocytes Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 May 2003, Vol. 101, No. 9, pp. 3699-3707 RED CELLS Iron transport by Nramp2/DMT1: pH regulation of transport by 2 histidines in transmembrane domain 6 Steven Lam-Yuk-Tseung, Gregory Govoni, John Forbes, and Philippe Gros From the Department of Biochemistry, McGill Cancer Center and Center for Host Resistance, McGill University, Montreal, QC. Mutations at natural resistance-associated macrophage protein 1 (Nramp1) impair phagocyte function and cause susceptibility to infections while mutations at Nramp2 (divalent metal transporter 1 [DMT1]) affect iron homeostasis and cause severe microcytic anemia. Structure-function relationships in the Nramp superfamily were studied by mutagenesis, followed by functional characterization in yeast and in mammalian cells. These studies identify 3 negatively charged and highly conserved residues in transmembrane domains (TM) 1, 4, and 7 as essential for cation transport by Nramp2/DMT1. The introduction of a charged residue (Gly185Arg) in TM4 found in the naturally occurring microcytic anemia mk (mouse) and Belgrade (rat) mutants is shown to cause a partial or complete loss of function in mammalian and yeast cells, respectively. A pair of mutation-sensitive and highly conserved histidines (His267, His272) was identified in TM6. Surprisingly, inactive His267 and His272 mutants could be rescued by lowering the pH of the transport assay. This indicates that His267/His272 are not directly involved in metal binding but, rather, play an important role in pH regulation of metal transport by Nramp proteins. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. Courville, E. 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