title: Identification of Ni-(L-His)₂ as a substrate for NikABCDE-dependent nickel uptake in Escherichia coli.
abstract: Nickel is an important cofactor for several microbial enzymes. The ATP-dependent NikABCDE transporter is one of several types of uptake pathways known to be important for nickel acquisition in microbes. The Escherichia coli NikA periplasmic binding protein is structurally homologous to the di- and oligopeptide binding proteins, DppA and OppA. This structural similarity raises interesting questions regarding the evolutionary relationships between the recognition of nickel ions and short peptides. We find that in defined minimal growth medium NikABCDE transports nickel ions in the presence of exogenously added L-histidine (L-His), but not D-histidine. Both nickel uptake in cells and nickel binding to purified NikA showed an L-His concentration dependence consistent with recognition of a Ni-(L-His)₂ complex. This discovery reveals parallels to the transport of other metal complexes, notably iron, and suggests the structural diversity of nickel transporters may arise from the need to recognize extracellular nickel complexed with different organic ligands, whether they be exogenously or endogenously produced. Further, these results suggest that experiments examining the physiology and ecology of nickel-requiring microbes should account for the possibility that the growth medium may not support nickel uptake.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA. pchivers@oberlin.edu
authors.forename: Peter T
authors.initials: PT
authors.lastname: Chivers
authors.forename: Erin L
authors.initials: EL
authors.lastname: Benanti
authors.forename: Vanessa
authors.initials: V
authors.lastname: Heil-Chapdelaine
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Iwig
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Rowe
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D006639:Histidine / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D009532:Nickel / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; D029968:Escherichia coli Proteins; C089849:nikA protein, E coli; D006639:Histidine; D009532:Nickel