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Origins of specificity and cross‐talk in metal ion sensing by B acillus subtilis Fur
Author(s) -
Ma Zhen,
Faulkner Melinda J.,
Helmann John D.
Publication year - 2012
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 - 10.1111/mmi.12049
Subject(s) - repressor , biology , binding site , dimer , metal , mutant , in vivo , biochemistry , homeostasis , dna , biophysics , stereochemistry , microbiology and biotechnology , chemistry , gene expression , genetics , gene , organic chemistry
Summary Fur ( f erric u ptake r egulator) is the master regulator of iron homeostasis in many bacteria, but how it responds specifically to Fe ( II ) in vivo is not clear. Biochemical analyses of B acillus subtilis Fur ( BsFur ) reveal that in addition to Fe ( II ), both Z n( II ) and Mn ( II ) allosterically activate BsFur – DNA binding. Dimeric BsFur co‐purifies with site 1 structural Zn ( II ) ( Fur 2 Zn 2 ) and can bind four additional Zn ( II ) or Mn ( II ) ions per dimer. Metal ion binding at previously described site 3 occurs with highest affinity, but the Fur 2 Zn 2 : Me 2 form has only a modest increase in DNA binding affinity (approximately sevenfold). Metallation of site 2 ( Fur 2 Zn 2 : Me 4 ) leads to a ∼ 150‐fold further enhancement in DNA binding affinity. Fe ( II ) binding studies indicate that BsFur buffers the intracellular F e( II ) concentration at ∼ 1 μ M . Both Mn ( II ) and Zn ( II ) are normally buffered at levels insufficient for metallation of BsFur site 2, thereby accounting for the lack of cross‐talk observed in vivo . However, in a perR mutant, where the BsFur concentration is elevated, BsFur may now use Mn ( II ) as a co‐repressor and inappropriately repress iron uptake. Since PerR repression of fur is enhanced by Mn ( II ), and antagonized by Fe ( II ), PerR may co‐regulate F e( II ) homeostasis by modulating BsFur levels in response to the Mn ( II )/ Fe ( II ) ratio.