2.A.52 The Ni2+-Co2+ Transporter (NiCoT) Family

Currently sequenced proteins of the NiCoT family are found in Gram-negative and Gram-positive bacteria as well as archaea and eukaryotes. The functionally best characterized members of the family catalyze uptake of Ni2+ and/or Co2+ in a proton motive force-dependent process. These proteins vary in size from 301 to 381 amino acyl residues and possess 7 or 8 TMSs. Topological analyses with the HoxN Ni2+ transporter of Ralstonia eutropha (Alcaligenes eutrophus) suggest that it possesses 8 TMSs with its N- and C-termini in the cytoplasm. The Co2+ (Ni2+) transporter of Rhodococcus rhodochrous, NhlF, exhibits eight putative TMSs, and eight apparent TMSs are revealed by a hydropathy analysis of the multiple alignment of the NiCoT family protein sequences. An HX4DH sequence in helix 2 of the HoxN protein has been implicated in Ni2+ binding, and both helix 1 and helix 2 which interact spatially, form the selectivity filter (Degan and Eitinger, 2002). In the H. pylori NixA homologue, several conserved motifs have been shown to be important for Ni2+ binding and transport (Wolfram and Bauerfeind, 2002).

The overall reaction catalyzed by the proteins of the NiCoT family is:

[Ni2+ or Co2+] (out) [Ni2+ or Co2+] (in)



This family belongs to the Transporter-Opsin-G protein-coupled receptor (TOG) Superfamily.

 

References:

Degen, O. and T. Eitinger. (2002). Substrate specificity of nickel/cobalt permeases: insights from mutants altered in transmembrane domains I and II. J. Bacteriol. 184: 3569-3577.

Degen, O., M. Kobayashi, S. Shimizu, and T. Eitinger. (1999). Selective transport of divalent cations by transition metal permeases: the Alcaligenes eutrophus HoxN and the Rhodococcus rhodochrous NhlF. Arch. Microbiol. 171: 139-145.

Deng, X., J. He, and N. He. (2013). Comparative study on Ni2+-affinity transport of nickel/cobalt permeases (NiCoTs) and the potential of recombinant Escherichia coli for Ni2+ bioaccumulation. Bioresour Technol 130: 69-74.

Eitinger, T. and B. Friedrich. (1991). Cloning, nucleotide sequence, and heterologous expression of a high-affinity nickel transport gene from Alcaligenes eutrophus. J. Biol. Chem. 266: 3222-3227.

Eitinger, T. and B. Friedrich. (1994). A topological model for the high affinity nickel transporter of Alcaligenes eutrophus. Mol. Microbiol. 12: 1025-1032.

Eitinger, T. and M.-A. Mandrand-Berthelot. (2000). Nickel transport systems in microorganisms. Arch. Microbiol. 173: 1-9.

Eitinger, T., L. Wolfram, O. Degen, and C. Anthon. (1997). A Ni2+ binding motif is the basis of high affinity transport of the Alcaligenes eutrophus nickel permease. J. Biol. Chem. 272: 17139-17144.

Eitinger, T., O. Degen, U. Böhnke, and M. Müller. (2000). Nic1p, a relative of bacterial transition metal permeases in Schizosaccharomyces pombe, provides nickel ion for urease biosynthesis. J. Biol. Chem. 275: 18029-18033.

Eitinger, T., O. Degen, U. Bohnke, and M. Muller. (2000). Nic1p, a relative of bacterial transition metal permeases in schizosaccharomyces pombe, provides nickel ion for urease biosynthesis. J. Biol. Chem. 275: 33184.

Fu, C., S. Javedan, F. Moshiri, and R.J. Maier. (1994). Bacterial genes involved in incorporation of nickel into hydrogenase enzyme. Proc. Natl. Acad. Sci. USA 91: 5099-5103.

Fulkerson, J.F., Jr. and H.L.T. Mobley. (2000). Membrane topology of the NixA nickel transporter of Helicobacter pylori: two nickel transport-specific motifs within transmembrane helices II and III. J. Bacteriol. 182: 1722-1730.

Hebbeln, P. and T. Eitinger. (2004). Heterologous production and characterization of bacterial nickel/cobalt permeases. FEMS Microbiol. Lett. 230: 129-135.

Iwig, J.S., J.L. Rowe, and P.T. Chivers. (2006). Nickel homeostasis in Escherichia coli - the rcnR-rcnA efflux pathway and its linkage to NikR function. Mol. Microbiol. 62: 252-262.

Komeda, H., M. Kobayashi, and S. Shimizu. (1997). A novel transporter involved in cobalt uptake. Proc. Natl. Acad. Sci. USA 94: 36-41.

Rodrigue, A., G. Effantin, and M.A. Mandrand-Berthelot. (2005). Identification of rcnA (yohM), a nickel and cobalt resistance gene in Escherichia coli. J. Bacteriol. 187: 2912-2916.

Saier, M.H., Jr., B.H. Eng, S. Fard, J. Garg, D.A. Haggerty, W.J. Hutchinson, D.L. Jack, E.C. Lai, H.J. Liu, D.P. Nusinew, A.M. Omar, S.S. Pao, I.T. Paulsen, J.A. Quan, M. Sliwinski, T.-T. Tseng, S. Wachi, and G.B. Young. (1999). Phylogenetic characterization of novel transport protein families revealed by genome analyses. Biochim. Biophys. Acta 1422: 1-56.

Wolfram, L. and P. Bauerfeind. (2002). Conserved low-affinity nickel-binding amino acids are essential for the function of the nickel permease NixA of Helicobacter pylori. J. Bacteriol. 184: 1438-1443.

Wolfram, L., B. Friedrich, and T. Eitinger. (1995). The Alcaligenes eutrophus protein HoxN mediates nickel transport in Escherichia coli. J. Bacteriol. 177: 1840-1843.

Wolfram, L., E. Haas, and P. Bauerfeind. (2006). Nickel represses the synthesis of the nickel permease NixA of Helicobacter pylori. J. Bacteriol. 188: 1245-1250.

Examples:

TC#NameOrganismal TypeExample
2.A.52.1.1

High affinity Ni2+-specific transporter, HoxN (Hebbeln and Eitinger 2004).

Bacteria

HoxN of Ralstonia eutropha

 
2.A.52.1.2

Co2+ transporter, NhlF (also transports Ni2+ with low affinity) (Hebbeln and Eitinger 2004).

Proteobacteria

NhlF of Rhodococcus rhodochrous

 
2.A.52.1.3

Ni2+ -specific transporter, Nic1p (Eitinger et al. 2000).

Yeast

Nic1p of Schizosaccharomyces pombe

 
2.A.52.1.4

High affinity Ni2+ uptake porter, NixA.  Transcription is regulated by NixR (Wolfram et al. 2006).

Bacteria

NixA of Helicobacter pylori

 
2.A.52.1.5

NisA of 350 aas and 8 TMSs (Hebbeln and Eitinger 2004; Deng et al. 2013).

Firmicutes

NisA of Staphylococcus aureus

 
2.A.52.1.6

HupN of 381 aas and 8 TMSs (Hebbeln and Eitinger 2004; Deng et al. 2013).

Proteobacteria

HupN of Brandyrhizobium japonicum

 
2.A.52.1.7

NicT of 372 aas and 8 TMSs.

Actinobacteria

NicT of Mycobacterium tuberculosis

 
2.A.52.1.8

Putative high affinity nickel ion uptake transporter of 413 aas and 8 TMSs

Fungi

Nickel transporter of Neurospora crassa

 
2.A.52.1.9

NicO homologue of 363 aas and 6 TMSs

Haptophyceae

NicO of Emailiania huxleyi

 
Examples:

TC#NameOrganismal TypeExample
2.A.52.2.1

Putative Ni2+/Co2+ uptake transporter of 277 aas and 7 TMSs.

Nitrospirae

Nickel/cobalt transporter of Leptospirillum ferroxidans

 
2.A.52.2.2

Putative Ni2+/Co2+ transporter of 269 aas and 7 TMSs.

Proteobacteria

Nickel/cobalt transporter of Dechloromonas aromatica

 
2.A.52.2.3

Putative Ni2+/Co2+ uptake porter of 220 aas and 6 TMSs.

Deinococcus/Thermus

Nickel/cobalt porter of Thermus thermophilus

 
2.A.52.2.4

Putative nickel/cobalt porter of 227 aas and 6 TMSs

Deinococcus/Thermus

Ni2+ porter of Deinococcus deserti

 
2.A.52.2.5

Putative transporter of 274 aas and 6 TMSs.

Bacteroidetes

Transporter of Chitinophaga pinensis

 
2.A.52.2.6

NiCoT homologue of 224 aas and 6 TMSs.

Cyanobacteria

NiCoT family member of Gloeobacter violaceus

 
Examples:

TC#NameOrganismal TypeExample
Examples:

TC#NameOrganismal TypeExample