PMID:21487006
| Citation |
Zomot, E and Bahar, I (2011) Protonation of glutamate 208 induces the release of agmatine in an outward-facing conformation of an arginine/agmatine antiporter. J. Biol. Chem. 286:19693-701 |
|---|---|
| Abstract |
Virulent enteric pathogens have developed several systems that maintain intracellular pH to survive extreme acidic conditions. One such mechanism is the exchange of arginine (Arg(+)) from the extracellular region with its intracellular decarboxylated form, agmatine (Agm(2+)). The net result of this process is the export of a virtual proton from the cytoplasm per antiport cycle. Crystal structures of the arginine/agmatine antiporter from Escherichia coli, AdiC, have been recently resolved in both the apo and Arg(+)-bound outward-facing conformations, which permit us to assess for the first time the time-resolved mechanisms of interactions that enable the specific antiporter functionality of AdiC. Using data from ∼1 μs of molecular dynamics simulations, we show that the protonation of Glu-208 selectively causes the dissociation and release of Agm(2+), but not Arg(+), to the cell exterior. The impact of Glu-208 protonation is transmitted to the substrate binding pocket via the reorientation of Ile-205 carbonyl group at the irregular portion of transmembrane (TM) helix 6. This effect, which takes place only in the subunits where Agm(2+) is released, invites attention to the functional role of the unwound portion of TM helices (TM6 Trp-202-Glu-208 in AdiC) in facilitating substrate translocation, reminiscent of the behavior observed in structurally similar Na(+)-coupled transporters. |
| Links |
PubMed PMC3103348 Online version:10.1074/jbc.M110.202085 |
| Keywords |
Agmatine/chemistry; Agmatine/metabolism; Amino Acid Transport Systems/chemistry; Amino Acid Transport Systems/genetics; Amino Acid Transport Systems/metabolism; Antiporters/chemistry; Antiporters/genetics; Antiporters/metabolism; Binding Sites; Biological Transport/physiology; Crystallography, X-Ray; Escherichia coli/chemistry; Escherichia coli/genetics; Escherichia coli/metabolism; Escherichia coli Proteins/chemistry; Escherichia coli Proteins/genetics; Escherichia coli Proteins/metabolism; Glutamic Acid/chemistry; Glutamic Acid/genetics; Glutamic Acid/metabolism; Models, Molecular; Protein Structure, Secondary |
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