Virulent enteric pathogens such as Escherichia coli strain O 157∶H7 rely on acid resistance (AR) systems to survive the acidic environment in the stomach.A major component of AR is an arginine-dependent arginine:agrnatine antiporter that expels intracellular protons.Here we report the crystal structure of AdiC, the arginine:agrnatine antiporter from E.coli O157∶H7, in both substrate-free and substrate-bound conformations.AdiC is a representative member of the amino acid polyamine organocation (APC) superfamily of transporters.AdiC contains 12 transmembrane segments, forms a homodimer, exists in an outward-open conformation in the absence of substrate binding, and in response to Arg binding,undergoes a major conformational switch to adopt an occluded conformation.Four hydrophobic amino acids and Glu208 are directly involved in substrate binding and transport.Structural and biochemical analysis reveals the essential transport residues,defines the transport route, and suggests a previously unreported mechanism for the antiporter activity.