Permeation Mechanism in the AmtB Ammonium Transporter: Putative Electrogenic Co-Transport of NH3 and H+

Abstract

Despite the growing amount of structural information, the molecular details of the mechanism by which membrane proteins of the Amt/Rh family mediate ammonium transport remain elusive. For instance, in protein AmtB from Escherichia coli, it is not known whether NH3 is diffusing passively through the protein pore or is involved in an NH3/H+ co-transport mechanism.Using state-of-the-art computational methods (polarizable force fields and hybrid QM/MM molecular dynamics simulations combined with free energy calculations) we investigate the thermodynamics and kinetics of various mechanisms for proton co-transport. Based on these simulations we propose a plausible NH3/H+ co-transport mechanism in which the twin-histidines dyad lining the pore plays a central role.