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).
Distant homologues of the NiCoT family (subfamily 2) have differing predicted topologies: 4, 5, 6, 7 and 8 TMSs. One such homologue, RcnA (YohM) of E. coli (274 aas) has 6 putative TMSs in a 3+3 arrangement with a large hydrophilic loop between putative TMSs 3 and 4. This protein is believed to catalyze Ca2+ and Ni2+ efflux (Rodrique et al., 2005). A close homologue of RcnA, NirC of Klebsiella oxytoca (307 aas) has 4 putative TMSs (1+3). Several homologues of RcnA (e.g., from Ralstonia solanacearum; CAD17703) have 7 putative TMSs (4+3). Still another homologue, UreH of Methanocaldococcus janaschii has 6 putative TMSs in a 1+2+2+1 arrangement. This apparent topological variation is not understood.
The overall reaction catalyzed by the proteins of subclass 1 of the NiCoT family is:
[Ni2+ or Co2+] (out) [Ni2+ or Co2+] (in).
The overall reaction catalyzed by proteins of subclass 2 of the NiCoT family is probably:
[Ni2+ or Co2+] (in) [Ni2+ or Co2+] (out).