2.A.27 The Glutamate:Na⁺ Symporter (ESS) Family

Two members of this family have been functionally characterized. Both permeases (called GltS) have 401-402 amino acyl residues with 12 putative α-helical transmembrane spanners. Evidence for a 10 TMS topology has been obtained using translational lacZ and phoA fusions. Both hydrophobic segments that did not prove to be TMSs were glycine-rich (4 or 5 glycines per segment) (Gal et al., 2002). The two domains, of 5 TMSs plus a reentrant or pore-loop each, suggest that these proteins along with CitS in the 2HCT family, (2.A.24) might be members of the 2HCT superfamily (Dobrowolski et al., 2007). The occurrence of these 'helix breaking' residues may account for their exclusion from the membrane.

GltS is a Na⁺-dependent secondary carrier that transports L- and D-glutamate as well as the toxic analogues α-methyl glutamate and homocysteate (Essenberg, 1984). Homologues are found in many diverse Gram-negative proteobacteria, Synechocystis and Staphylococcus aureus. The family is thus widespread in bacteria but not in archaea or eukaryotes.

Dobrowolski and Lolkema (2009) have pointed to structural and mechanistic similarities between the ESS (TC #2.A.27) and 2-HCT (TC #2.A.24) transporters, as well as the two domain structure of the transporters and the presence and functional importance of the reentrant loops present in both domains. They propose that the conserved GGXG motifs are at the vertex of the reentrant loops.

The transport reaction catalyzed is:

glutamate (out) + Na⁺ (out) → glutamate (in) + Na⁺ (in)