Structure of a prokaryotic virtual proton pump at 3.2 A resolution

Nature. 2009 Aug 20;460(7258):1040-3. doi: 10.1038/nature08201. Epub 2009 Jul 5.


To reach the mammalian gut, enteric bacteria must pass through the stomach. Many such organisms survive exposure to the harsh gastric environment (pH 1.5-4) by mounting extreme acid-resistance responses, one of which, the arginine-dependent system of Escherichia coli, has been studied at levels of cellular physiology, molecular genetics and protein biochemistry. This multiprotein system keeps the cytoplasm above pH 5 during acid challenge by continually pumping protons out of the cell using the free energy of arginine decarboxylation. At the heart of the process is a 'virtual proton pump' in the inner membrane, called AdiC, that imports L-arginine from the gastric juice and exports its decarboxylation product agmatine. AdiC belongs to the APC superfamily of membrane proteins, which transports amino acids, polyamines and organic cations in a multitude of biological roles, including delivery of arginine for nitric oxide synthesis, facilitation of insulin release from pancreatic beta-cells, and, when inappropriately overexpressed, provisioning of certain fast-growing neoplastic cells with amino acids. High-resolution structures and detailed transport mechanisms of APC transporters are currently unknown. Here we describe a crystal structure of AdiC at 3.2 A resolution. The protein is captured in an outward-open, substrate-free conformation with transmembrane architecture remarkably similar to that seen in four other families of apparently unrelated transport proteins.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Transport Systems / chemistry*
  • Amino Acid Transport Systems / metabolism
  • Antiporters / chemistry*
  • Antiporters / metabolism
  • Bacterial Proteins / chemistry*
  • Crystallography, X-Ray
  • Escherichia coli / chemistry*
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Multigene Family
  • Protein Conformation
  • Salmonella typhi / chemistry*
  • Structural Homology, Protein


  • AdiC protein, E coli
  • Amino Acid Transport Systems
  • Antiporters
  • Bacterial Proteins
  • Escherichia coli Proteins

Associated data

  • PDB/3HQK