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Origins of metal ion selectivity in the DtxR/MntR family of metalloregulators
Author(s) -
Guedon Emmanuel,
Helmann John D.
Publication year - 2003
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1046/j.1365-2958.2003.03445.x
Subject(s) - bacillus subtilis , corynebacterium diphtheriae , repressor , biology , mutant , diphtheria toxin , biochemistry , gene , microbiology and biotechnology , gene expression , genetics , toxin , bacteria , vaccination , immunology , diphtheria
Summary Corynebacterium diphtheriaeDtxR 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 inBacillus subtilis. When expressed inB. 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 afurmutant 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 inB. subtilis, and the effects of afur mutation, demonstrate that cellular milieu also influences metal responsiveness.