Ammonium transporters achieve charge transfer by fragmenting their substrate.
Proteins of the Amt/MEP family facilitate ammonium transport across the membranes of plants, fungi, and bacteria and are essential for growth in nitrogen-poor environments. Some are known to facilitate the diffusion of the neutral NH(3), while others, notably in plants, transport the positively charged NH(4)(+). On the basis of the structural data for AmtB from Escherichia coli , we illustrate the mechanism by which proteins from the Amt family can sustain electrogenic transport. Free energy calculations show that NH(4)(+) is stable in the AmtB pore, reaching a binding site from which it can spontaneously transfer a proton to a pore-lining histidine residue (His168). The substrate diffuses down the pore in the form of NH(3), while the excess proton is cotransported through a highly conserved hydrogen-bonded His168-His318 pair. This constitutes a novel permeation mechanism that confers to the histidine dyad an essential mechanistic role that was so far unknown.
Department of Chemistry and Biochemistry and Centre for Research in Molecular Modeling (CERMM), Concordia University, 7141 Sherbrooke Street West, Montréal, Québec H4B 1R6, Canada.
Shihao
S
Wang
Esam A
EA
Orabi
Sefer
S
Baday
Simon
S
Bernèche
Guillaume
G
Lamoureux
D001665:Binding Sites; D027682:Cation Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D008954:Models, Biological; D056004:Molecular Dynamics Simulation; D011789:Quantum Theory; D000644:Quaternary Ammonium Compounds / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
D027682:Cation Transport Proteins; D000644:Quaternary Ammonium Compounds