4DJI

Structure of glutamate-GABA antiporter GadC

Summary for 4DJI

• Entry DOI: 10.2210/pdb4dji/pdb
• Related: 4DJK
• Descriptor: Probable glutamate/gamma-aminobutyrate antiporter (1 entity in total)
• Functional Keywords: leut fold, glutamate-gaba antiporter, transport protein
• Biological source: Escherichia coli
• Cellular location: Cell inner membrane; Multi-pass membrane protein: P63235
• Total number of polymer chains: 2
• Total formula weight: 110228.42

Authors

Ma, D.,Lu, P.L.,Yan, C.Y.,Fan, C.,Yin, P.,Wang, J.W.,Shi, Y.G. (deposition date: 2012-02-02, release date: 2012-03-14, Last modification date: 2024-03-20)

Primary citation

Ma, D.,Lu, P.L.,Yan, C.Y.,Fan, C.,Yin, P.,Wang, J.W.,Shi, Y.G.
Structure and mechanism of a glutamate-GABA antiporter
Nature, 483:632-636, 2012

PubMed Abstract: Food-borne hemorrhagic Escherichia coli, exemplified by the strains O157:H7 and O104:H4 (refs 1, 2), require elaborate acid-resistance systems (ARs) to survive the extremely acidic environment such as the stomach (pH ≈ 2). AR2 expels intracellular protons through the decarboxylation of L-glutamate (Glu) in the cytoplasm and exchange of the reaction product γ-aminobutyric acid (GABA) with extracellular Glu. The latter process is mediated by the Glu-GABA antiporter GadC, a representative member of the amino-acid-polyamine-organocation superfamily of membrane transporters. The functional mechanism of GadC remains largely unknown. Here we show, with the use of an in vitro proteoliposome-based assay, that GadC transports GABA/Glu only under acidic conditions, with no detectable activity at pH  values higher than 6.5. We determined the crystal structure of E. coli GadC at 3.1 Å resolution under basic conditions. GadC, comprising 12 transmembrane segments (TMs), exists in a closed state, with its carboxy-terminal domain serving as a plug to block an otherwise inward-open conformation. Structural and biochemical analyses reveal the essential transport residues, identify the transport path and suggest a conserved transport mechanism involving the rigid-body rotation of a helical bundle for GadC and other amino acid antiporters.

PubMed: 22407317
DOI: 10.1038/nature10917

Experimental method

X-RAY DIFFRACTION (3.187 Å)