Schematic representation of the glutamate transporter transport cycle. (A) EAATs couple glutamate uptake to symport of three sodium ions and one proton and to antiport of one potassium ion. (B) The archaeal homologues Glt_Tk and Glt_Ph couple aspartate uptake only to symport of three sodium ions. Both mammalian and archaeal homologues were shown to support chloride conductance uncoupled to substrate transport. One protomer of the homotrimeric protein is depicted schematically in the membrane plane. The scaffold and transport domains are shown in yellow and blue, respectively; the position of membrane is indicated with the black lines, where “in” and “out” stand for inside and outside the cell, respectively. Sodium (magenta), proton (dark green), chloride (gray), and potassium (light green) ions are shown as circles, and substrate as a purple triangle. Possible chloride ion pathway is depicted with a dashed arrow.