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2.A.11 The Citrate-Mg2+:H+ (CitM) Citrate-Ca2+:H+ (CitH) Symporter (CitMHS) Family

The two characterized members of the CitMHS family are both citrate uptake permeases from Bacillus subtilis. CitM is believed to transport a citrate2--Mg2+ complex in symport with one H+ per Mg2+-citrate while CitH apparently transports a citrate2--Ca2+ complex in symport with protons (Boorsma et al., 1996; Krom et al., 2000). The cation specificity of CitM is: Mg2+, Mn2+, Ba2+, Ni2+, Co2+, Ca2+ and Zn2+ with an order of preference in this order. CitM is highly specific for citrate and D-isocitrate and does not transport other di- and tri-carboxylates including succinate, L-isocitrate, cis-aconitate and tricarballylate (Li and Pajor, 2002; Warner and Lolkema, 2002). For CitH, the cation specificity (in order of preference) is: Ca2+, Ba2+ and Sr2+ (Krom et al., 2000). The two proteins are 60% identical, contain about 400 amino acyl residues and possess twelve putative transmembrane spanners. A CitM homologue in S. mutans transports citrate conjugated to Fe2+ or Mn2+ but not Ca2+, Mg2+ or Ni2+ (Korithoski et al., 2005).

The CitMHS family belongs within the IT superfamily (Prakash et al., 2003; Rabus et al., 1999). Members of this family are found in Gram-positive and Gram-negative bacteria, archaea and possibly in eukaryotes. These proteins all probably arose by an internal gene duplication event. Lensbouer & Doyle (2010) have reviewed these systems. They classify the porters with three superfamilies, according to ion-preference: 1) Mg2+-preferring, 2) Ca2+-preferring, and 3) Fe2+-preferring . These authors provide information about transcriptional control, putative structure, predicted family members, members characterized to date and potential use in bioremediation.

The transport reactions catalyzed by (1) CitM and (2) CitH, respectively, are:

(1) Citrate • Mg (out) + nH+ (out) ⇌ Citrate • Mg (in) + nH+ (in)

(2) Citrate (out) + nH+ (out) ⇌ Citrate (in) + nH+

(3) Citrate • Ca2+ (out) + nH+ (out) ⇌ Citrate • Ca2+ (in) + nH+ (in)

This family belongs to the: IT Superfamily.

References associated with 2.A.11 family:

Boorsma, A., M.E. van der Rest, J.S. Lolkema, and W.N. Konings. (1996). Secondary transporters for citrate and the Mg2+-citrate complex in Bacillus subtilis are homologous proteins. J. Bacteriol. 178: 6216-6222. 8892821
Brocker, M., S. Schaffer, C. Mack, and M. Bott. (2009). Citrate utilization by Corynebacterium glutamicum is controlled by the CitAB two-component system through positive regulation of the citrate transport genes citH and tctCBA. J. Bacteriol. 191: 3869-3880. 19376865
Korithoski, B., K. Krastel, and D.G. Cvitkovitch. (2005). Transport and metabolism of citrate by Streptococcus mutans. J. Bacteriol. 187: 4451-4456. 15968054
Krom, B.P., J.B. Warner, W.N. Konings, and J.S. Lolkema. (2000). Complementary metal ion specificity of the metal-citrate transporters CitM and CitH of Bacillus subtilis. J. Bacteriol. 182: 6374-6381. 11053381
Lensbouer, J.J. and R.P. Doyle. (2010). Secondary transport of metal-citrate complexes: the CitMHS family. Crit. Rev. Biochem. Mol. Biol. 45: 453-462. 20735204
Lensbouer, J.J., A. Patel, J.P. Sirianni, and R.P. Doyle. (2008). Functional characterization and metal ion specificity of the metal-citrate complex transporter from Streptomyces coelicolor. J. Bacteriol. 190: 5616-5623. 18556792
Li, H. and A.M. Pajor. (2002). Functional characterization of CitM, the Mg2+-citrate transporter. J. Membr. Biol. 185: 9-16. 11891560
Prakash, S., G. Cooper, S. Singhi, and M.H. Saier, Jr. (2003). The ion transporter superfamily. Biochim. Biophys. Acta 1618: 79-92. 14643936
Rabus, R., D.L. Jack, D.J. Kelly, and M.H. Saier Jr. (1999). TRAP transporters: an ancient family of extracytoplasmic solute-receptor-dependent secondary active transporters. Microbiology 145: 3431-3445. 10627041
Repizo, G.D., V.S. Blancato, P.D. Sender, J. Lolkema, and C. Magni. (2006). Catabolite repression of the citST two-component system in Bacillus subtilis. FEMS Microbiol. Lett. 260: 224-231. 16842348
Somers, J.M. and W.W. Kay. (1983). Genetic fine structure of the tricarboxylate transport (tct) locus of Salmonella typhimurium. Mol. Gen. Genet. 190: 20-26. 6134229
Sweet, G.D., C.M. Kay, and W.W. Kay. (1984). Tricarboxylate-binding proteins of Salmonella typhimurium. Purification, crystallization, and physical properties. J. Biol. Chem. 259: 1586-1592. 6141166
Warner, J.B. and J.S. Lolkema. (2002). Growth of Bacillus subtilis on citrate and isocitrate is supported by the Mg2+-citrate transporter CitM. Microbiology 148: 3405-3412. 12427932
Yamamoto, H., M. Murata, and J. Sekiguchi. (2000). The CitST two-component system regulates the expression of the Mg-citrate transporter in Bacillus subtilis. Mol. Microbiol. 37: 898-912. 10972810