title: Origins of metal ion selectivity in the DtxR/MntR family of metalloregulators.
abstract: Corynebacterium diphtheriae DtxR is an iron-specific repressor of diphtheria toxin expression and iron homeostasis functions. A homologue, MntR, serves as a manganese-specific repressor of Mn(II) uptake in Bacillus subtilis. When expressed in B. subtilis, DtxR regulates gene expression in response to either iron or manganese with comparable sensitivity. Replacement of two amino acids in the metal-sensing site with the corresponding residues from MntR results in a DtxR mutant that is highly selective for Mn(II). However, iron responsiveness can be partially restored in a fur mutant in which iron uptake is derepressed and intracellular iron pools elevated. Conversely, if the putative metal-binding residues in MntR are altered to those in DtxR, the resulting protein responds to both iron and manganese. These results suggest that the composition and geometry of the metal-binding site plays a major role in defining the metal-selectivity in this protein family. However, the broadened selectivity of DtxR when expressed in B. subtilis, and the effects of a fur mutation, demonstrate that cellular milieu also influences metal responsiveness.
authors.affiliation: Department of Microbiology, Cornell University, Ithaca, NY 14853-8101, USA.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Guedon
authors.forename: John D
authors.initials: JD
authors.lastname: Helmann
mesh_terms: D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D003353:Corynebacterium diphtheriae / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008345:Manganese / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C075586:DtxR protein, Corynebacterium diphtheriae; C433792:MntR protein, bacteria; D012097:Repressor Proteins; D008345:Manganese; D007501:Iron