5J4N

Crystal structure of the L-arginine/agmatine antiporter AdiC in complex with agmatine at 2.6 Angstroem resolution

Summary for 5J4N

• Entry DOI: 10.2210/pdb5j4n/pdb
• Descriptor: Arginine/agmatine antiporter, AGMATINE (3 entities in total)
• Functional Keywords: membrane protein, exchanger, transporter, adic-agmatine complex, transport protein
• Biological source: Escherichia coli O157:H7
• Cellular location: Cell inner membrane ; Multi- pass membrane protein : P60063
• Total number of polymer chains: 2
• Total formula weight: 95943.16

Authors

Jeckelmann, J.M.,Ilgue, H.,Fotiadis, D. (deposition date: 2016-04-01, release date: 2016-08-31, Last modification date: 2024-01-10)

Primary citation

Ilgu, H.,Jeckelmann, J.M.,Gapsys, V.,Ucurum, Z.,de Groot, B.L.,Fotiadis, D.
Insights into the molecular basis for substrate binding and specificity of the wild-type L-arginine/agmatine antiporter AdiC.
Proc.Natl.Acad.Sci.USA, 113:10358-10363, 2016

PubMed Abstract: Pathogenic enterobacteria need to survive the extreme acidity of the stomach to successfully colonize the human gut. Enteric bacteria circumvent the gastric acid barrier by activating extreme acid-resistance responses, such as the arginine-dependent acid resistance system. In this response, l-arginine is decarboxylated to agmatine, thereby consuming one proton from the cytoplasm. In Escherichia coli, the l-arginine/agmatine antiporter AdiC facilitates the export of agmatine in exchange of l-arginine, thus providing substrates for further removal of protons from the cytoplasm and balancing the intracellular pH. We have solved the crystal structures of wild-type AdiC in the presence and absence of the substrate agmatine at 2.6-Å and 2.2-Å resolution, respectively. The high-resolution structures made possible the identification of crucial water molecules in the substrate-binding sites, unveiling their functional roles for agmatine release and structure stabilization, which was further corroborated by molecular dynamics simulations. Structural analysis combined with site-directed mutagenesis and the scintillation proximity radioligand binding assay improved our understanding of substrate binding and specificity of the wild-type l-arginine/agmatine antiporter AdiC. Finally, we present a potential mechanism for conformational changes of the AdiC transport cycle involved in the release of agmatine into the periplasmic space of E. coli.

PubMed: 27582465
DOI: 10.1073/pnas.1605442113

Experimental method

X-RAY DIFFRACTION (2.594 Å)