title: Femtomolar sensitivity of metalloregulatory proteins controlling zinc homeostasis.
abstract: Intracellular zinc is thought to be available in a cytosolic pool of free or loosely bound Zn(II) ions in the micromolar to picomolar range. To test this, we determined the mechanism of zinc sensors that control metal uptake or export in Escherichia coli and calibrated their response against the thermodynamically defined free zinc concentration. Whereas the cellular zinc quota is millimolar, free Zn(II) concentrations that trigger transcription of zinc uptake or efflux machinery are femtomolar, or six orders of magnitude less than one atom per cell. This is not consistent with a cytosolic pool of free Zn(II) and suggests an extraordinary intracellular zinc-binding capacity. Thus, cells exert tight control over cytosolic metal concentrations, even for relatively low-toxicity metals such as zinc.
authors.affiliation: Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Outten
authors.forename: T V
authors.initials: TV
authors.lastname: O'Halloran
mesh_terms: D001426:Bacterial Proteins; D001483:Base Sequence; D003470:Culture Media; D003600:Cytosol / Q000378:metabolism; D018983:DNA Footprinting; D004269:DNA, Bacterial / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029968:Escherichia coli Proteins; D005029:Ethylenediamines / Q000378:metabolism; D005798:Genes, Bacterial; D006706:Homeostasis; D006863:Hydrogen-Ion Concentration; D017136:Ion Transport; D008969:Molecular Sequence Data; D009994:Osmolar Concentration; D011401:Promoter Regions, Genetic; D013816:Thermodynamics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015032:Zinc / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D003470:Culture Media; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D005029:Ethylenediamines; D014157:Transcription Factors; C492246:ZntR protein, E coli; C118628:ZntR protein, bacteria; C114819:Zur protein, E coli; D012321:DNA-Directed RNA Polymerases; D003850:Deoxyribonuclease I; D015032:Zinc; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine