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2.A.51 The Chromate Ion Transporter (CHR) Family

Homologues of the CHR family have been identified in bacteria, eukaryotes and archaea. Two Bacillus homologues are half length with six putative TMSs each (Nies et al., 1998). These two proteins together (2.A.51.1.5), but not singly, cause chromate resistance due to formation of a heterodimer and consequent chromate efflux (Díaz-Magaña et al., 2009). Half-sized homologues are found in several bacteria. The functionally characterized chromate efflux pumps of P. aeruginosa and A. eutrophus are plasmid-encoded. They are about 400 amino acyl residues long with 10 putative transmembrane α-helical spanners (TMSs). They arose by a tandem internal gene duplication event from a putative 6 TMS primordial precursor, but the first two TMSs in the A. entrophus ChrA protein have lost their hydrophobic character (Nies et al., 1998).

In a more recent study (Diaz-Perez et al., 2007), 77 duplicated 'bidomains' (BDs) and 58 unduplicated 'monodomains' (MDs) were identified and analyzed. The MDs clustered separately from the N-terminal BDs, and both clustered separately from the C-terminal BDs. This suggests that the MDs, possibly present in inverted orientation in the membrane, may have a unique structure and mode of action (Diaz-Perez et al., 2007).

The membrane topology of the ChrA protein of P. aeruginosa was conducted using lacZ and phoA translational fusions (Jiminez-Mejia et al., 2006). A 13 TMS topology was predicted with the N-terminus in the cytoplasm and the C-terminus in the periplasm. Predicted TMSs 1-6 proved to be homologous to predicted TMSs 8-13, but with opposite orientation in the membrane.

Synechococcus sp. PCC7942 bears an endogenous 50 Kb plasmid-encoded, sulfur-regulated CHR homologue that apparently confers chromate sensitivity (rather than chromate resistance) when grown in media containing a low sulfate concentration. This protein, designated SrpC, may be a sulfate uptake permease that can also transport chromate, but this possibility has not been established. ChrA of P. aeruginosa is a secondary carrier which might function by chromate uniport, chromate:H+ antiport, or chromate:anion antiport. It catalyzes CrO4 efflux with a Km of 80 μM. SO4= and MoO4= inhibit efflux but arsenate and vanadate do not inhibit (Pimentel et al., 2002). A pmf dependency is likely since valinomycin, nigericin and protonophores such as CCCP inhibit. Ramírez-Díaz et al. (2008) have published a review concerning the mechanisms of bacterial resistance to chromium compounds. In Neurosporal crassa, a chromate uptake transporter, Chr-1, a member of the Chr family, has been described (Flores-Alvarez et al. 2012).

Carbonic anhydrases (CAs) and their synergy with acid-base transporters play important roles in urinary acid secretion, the largest component of which is the reabsorption of HCO3- in specific nephron segments (Lee et al. 2023). Among these transporters are the Na+-coupled HCO3- transporters (NCBTs) and the Cl--HCO3- exchangers (AEs)-members of the SLC4 family. All of these transporters have traditionally been regarded as 'HCO3-' transporters, but two of the NCBTs carry CO32- rather than HCO3- and possibly all NCBTs follow suit. The role of CAs and 'HCO3-' transporters of the SLC4 family in renal acid-base physiology has been considered, and how these findings impact renal acid secretion have been discussed (Lee et al. 2023). Traditionally, investigators have associated CAs with producing or consuming solutes (CO2, HCO3-, and H+) and thus ensuring their efficient transport across cell membranes. In the case of CO32- transport by NCBTs, the role of membrane-associated CAs is not the production or consumption of substrates but the minimization of pH changes in nanodomains near the membrane.

The generalized transport reaction catalyzed by prokaryotic CHRs may be:

CrO42- (in) [+ nH+ (out)] → CrO42- (out) [+ nH+ (in)]

The generalized transport reaction catalyzed by SrpC or Chr-1 may be:

SO42- or CrO42- (out) + nH+ (out) → SO42- or CrO42- (in) + nH+ (in)

References associated with 2.A.51 family:

Aguilar-Barajas, E., E. Paluscio, C. Cervantes, and C. Rensing. (2008). Expression of chromate resistance genes from Shewanella sp. strain ANA-3 in Escherichia coli. FEMS Microbiol. Lett. 285: 97-100. 18537831
Aguilera, S., M.E. Aguilar, M.P. Chávez, J.E. López-Meza, M. Pedraza-Reyes, J. Campos-García, and C. Cervantes. (2004). Essential residues in the chromate transporter ChrA of Pseudomonas aeruginosa. FEMS Microbiol. Lett. 232: 107-112. 15019742
Alvarez, A.H., R. Moreno-Sánchez, and C. Cervantes. (1999). Chromate efflux by means of the ChrA chromate resistance protein from Pseudomonas aeruginosa. J. Bacteriol. 181: 7398-7400. 10572148
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Diaz-Magana A., Aguilar-Barajas E., Moreno-Sanchez R., Ramirez-Diaz MI., Riveros-Rosas H., Vargas E. and Cervantes C. (2009). Short-chain chromate ion transporter proteins from Bacillus subtilis confer chromate resistance in Escherichia coli. J Bacteriol. 191(17):5441-5. 19581367
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Jimenez-Mejia, R., J. Campos-Garcia, and C. Cervantes. (2006). Membrane topology of the chromate transporter ChrA of Pseudomonas aeruginosa. FEMS Microbiol. Lett. 262: 178-184. 16923073
Lee, S.K., W.F. Boron, and R. Occhipinti. (2023). Potential Novel Role of Membrane-Associated Carbonic Anhydrases in the Kidney. Int J Mol Sci 24:. 36835660
Martínez-Valencia, R., G. Reyes-Cortés, M.I. Ramírez-Díaz, H. Riveros-Rosas, and C. Cervantes. (2012). Antiparallel membrane topology of paired short-chain chromate transport proteins in Bacillus subtilis. FEMS Microbiol. Lett. 336: 113-121. 22900751
Nicholson, M.L. and D.E. Laudenbach. (1995). Genes encoded on a cyanobacterial plasmid are transcriptionally regulated by sulfur availability and CysR. J. Bacteriol. 177: 2143-2150. 7536734
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Nies, D.H. and S. Silver. (1995). Ion efflux systems involved in bacterial metal resistances. J. Indus. Microbiol. 14: 186-199. 7766211
Pimentel, B.E., R. Moreno-Sanchez, and C. Cervantes. (2002). Efflux of chromate by Pseudomonas aeruginosa cells expressing the ChrA protein. FEMS Microbiol. Lett. 212: 249-254. 12113942
Ramírez-Díaz, M.I., C. Díaz-Pérez, E. Vargas, H. Riveros-Rosas, J. Campos-García, and C. Cervantes. (2008). Mechanisms of bacterial resistance to chromium compounds. Biometals 21: 321-332. 17934697