title: Structure of a prokaryotic virtual proton pump at 3.2 A resolution.
abstract: 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.
authors: Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, Massachusetts 02454, USA.
authors: Yiling
authors: Y
authors: Fang
authors: Hariharan
authors: H
authors: Jayaram
authors: Tania
authors: T
authors: Shane
authors: Ludmila
authors: L
authors: Kolmakova-Partensky
authors: Fang
authors: F
authors: Wu
authors: Carole
authors: C
authors: Williams
authors: Yong
authors: Y
authors: Xiong
authors: Christopher
authors: C
authors: Miller
mesh_terms: D000595:Amino Acid Sequence; D026905:Amino Acid Transport Systems / Q000737:chemistry* / Q000378:metabolism; D017920:Antiporters / Q000737:chemistry* / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000737:chemistry*; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family; D011487:Protein Conformation; D012485:Salmonella typhi / Q000737:chemistry*; D040681:Structural Homology, Protein
chemical_list: C476528:AdiC protein, E coli; D026905:Amino Acid Transport Systems; D017920:Antiporters; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins