Originally published in Science Express on 28 May 2009
Science 19 June 2009:
Vol. 324. no. 5934, pp. 1565 - 1568
DOI: 10.1126/science.1173654

Structure and Mechanism of an Amino Acid Antiporter

Xiang Gao,1,2,* Feiran Lu,1,2,* Lijun Zhou,1,2,* Shangyu Dang,1,2 Linfeng Sun,1,2 Xiaochun Li,1,2 Jiawei Wang,1,2 Yigong Shi2,3,

1 State Key Laboratory of Bio-membrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, China.
2 Center for Structural Biology, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China.
3 School of Medicine, Tsinghua University, Beijing 100084, China.
* These authors contributed equally to this work.

To whom correspondence should be addressed. E-mail: shi-lab@tsinghua.edu.cn

Virulent enteric pathogens such as Escherichia coli strain O157: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:agmatine antiporter that expels intracellular protons. Here, we report the crystal structure of AdiC, the arginine:agmatine antiporter from E. coli O157:H7 and a member of the amino acid/polyamine/organocation (APC) superfamily of transporters at 3.6 Å resolution. The overall fold is similar to that of several Na+-coupled symporters. AdiC contains 12 transmembrane segments, forms a homodimer, and exists in an outward-facing, open conformation in the crystals. A conserved, acidic pocket opens to the periplasm. Structural and biochemical analysis reveals the essential ligand-binding residues, defines the transport route, and suggests a conserved mechanism for the antiporter activity.