2.A.80 The Tripartite Tricarboxylate Transporter (TTT) Family
A single member of the TTT family has been both functionally characterized and sequenced, the TctABC transporter of Salmonella typhimurium. This system includes three components: TctA, a large (504 aa) transmembrane protein with 12 predicted TMSs, TctB, a small (144 aa) transmembrane protein with 4 putative TMSs, and TctC, a periplasmic tricarboxylate-binding receptor (325 aas). In these respects, TctABC resembles DctMQP of the TRAP-T family (TC #2.A.56). However, there is little or no significant sequence similarity between these two systems or between members of the two different families. TctC shows some sequence and motif similarities to the phosphonate (and other) binding receptors of bacteria (Tam and Saier, 1993). The homologues of these three proteins are found in Gram-negative bacteria, Gram-positive bacteria, and archaea. TctA homologues are the most conserved components of Tct family systems while TctB homologues are the least conserved.
All TctA homologues exhibit a well-conserved motif:
(Hy)6 G (Hy)3 G* (Hy)3 G* (Hy)2 P* G* (Hy)
(Hy = a hydrophobic residue; * = a fully conserved residue.)
This motif comprises TMS 1, but it can also be found, less well conserved, in TMS 7. This fact suggests that these proteins arose by an internal gene duplication event where a 6 TMS-encoding element duplicated to give a 12 TMS-encoding gene.
TctC has been purified and studied (Sweet et al., 1979, 1984). It binds fluorocitrate, citrate, isocitrate and cis-aconitate with micromolar affinities and decreasing affinities in that order. Binding of citrate to this dimeric protein proved to be Na+-dependent while divalent cations (Zn2+, Mg2+ and Co2+) were inhibitory (Sweet et al., 1979). TctC homologues are found in large numbers of species of Bordetella and other
The generalized transport reaction probably catalyzed by TctABC is:
Tricarboxylate (out) + nNa+ (out)