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Structural Determinants of Metal Selectivity in Prokaryotic Metal-responsive Transcriptional Regulators

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Abstract

Metal ion homeostasis in prokaryotes is maintained by metal-responsive transcriptional regulatory proteins that regulate the transcription of genes encoding proteins responsible for metal detoxification, sequestration, efflux and uptake. These metalloregulatory, or metal sensor proteins, bind a wide range of specific metal ions directly; this in turn, allosterically regulates (enhances or decreases) operator/promoter binding affinity or promoter structure. Recent structural studies reveal five distinct families of metal sensor proteins. The MerR and ArsR/SmtB families regulate the expression of genes required for metal ion detoxification, efflux and sequestration; here, metal binding leads to activation (MerR) or derepression (ArsR/SmtB) of the resistance operon. In contrast, the DtxR, Fur, and NikR families regulate genes encoding proteins involved in metal ion uptake; in these cases, the metal ion functions as a co-repressor in turning off uptake genes under metal-replete conditions. Inspection of the structures of representative members from each metal sensor family reveals several common characteristics: (1) they function as homo-oligomers (either dimers or tetramers); (2) metal-binding ligands are found at subunit interfaces, with ligands derived from more than one protomer; this likely helps drive quaternary structural changes that mediate allosteric coupling between the metal and DNA binding sites; and (3) the primary determinant of metal ion selectivity within each protein family is dictated by the coordination geometry of the metal chelate, with trends consistent with expectations from fundamental inorganic chemistry. This review highlights recent efforts to elucidate the structure of metal sensing chelates and the molecular mechanisms of allosteric coupling in metal sensor proteins.

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  1. Department of Biochemistry and Biophysics, Texas A&M University, 2128 TAMU, 77843-2128, College Station, Texas, USA

    Mario A. Pennella & David P. Giedroc

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  1. Mario A. Pennella
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  2. David P. Giedroc
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Correspondence to David P. Giedroc.

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Pennella, M., Giedroc, D. Structural Determinants of Metal Selectivity in Prokaryotic Metal-responsive Transcriptional Regulators. Biometals 18, 413–428 (2005). https://doi.org/10.1007/s10534-005-3716-8

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