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

The two initially characterized members of the CitMHS family are both citrate uptake permeases from Bacillus subtilis. CitM is believed to transport a citrate^2--Mg²⁺ complex in symport with one H⁺ per Mg²⁺-citrate while CitH apparently transports a citrate^2--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. However, Panchal et al. 2023 have concluded that there are three types of CitMHS transporters, oall that transports citate, but one preferentially with Mg²⁺, one with Ca²⁺, and one with Fe²⁺.  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 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, and (3) other members of the family, respectively, are:

(1) Citrate • Mg²⁺ (out) + nH⁺ (out) ⇌ Citrate • Mg²⁺ (in) + nH⁺ (in)

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

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