FIGURE 5.

Proposed mechanism of pH-dependent substrate transport by GadC. A, GadC is inactive at neutral pH. Most of the substrate molecules (Glu and GABA) are deprotonated, thus are unfavorable for transport. In addition, the substrate transport path is blocked by the C-plug of GadC. Under these conditions, no substrate exchange occurs. B, GadC is activated at acidic pH. When the extracellular pH is extremely acidic (pH 2∼3), the cytoplasmic pH in E. coli drops to a value between 3.5 and 5.0. In the cytoplasm, GABA exists in two forms, with no net charge (GABA⁰) and with one positive charge (GABA⁺), whereas the majority of Glu in the extracellular space carries no net charge (Glu⁰). At acidic pH, the C-plug of GadC may be displaced, allowing influx of Glu⁰ and efflux of GABA⁺.