Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom
Giulia Tamburrino
Computational Biology, School of Life Sciences, University of Dundee, Dundee, United Kingdom; Physics, School of Science and Engineering, University of Dundee, Dundee, United Kingdom
Adriana Bizior
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom
Marcus G Bage
Computational Biology, School of Life Sciences, University of Dundee, Dundee, United Kingdom; Physics, School of Science and Engineering, University of Dundee, Dundee, United Kingdom
Computational Biology, School of Life Sciences, University of Dundee, Dundee, United Kingdom; Physics, School of Science and Engineering, University of Dundee, Dundee, United Kingdom
Computational Biology, School of Life Sciences, University of Dundee, Dundee, United Kingdom
Eilidh Terras
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom
Paul A Hoskisson
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom
Anna Maria Marini
Biology of Membrane Transport Laboratory, Department of Molecular Biology, Université Libre de Bruxelles, Gosselies, Belgium
Ulrich Zachariae
Computational Biology, School of Life Sciences, University of Dundee, Dundee, United Kingdom; Physics, School of Science and Engineering, University of Dundee, Dundee, United Kingdom
The transport of charged molecules across biological membranes faces the dual problem of accommodating charges in a highly hydrophobic environment while maintaining selective substrate translocation. This has been the subject of a particular controversy for the exchange of ammonium across cellular membranes, an essential process in all domains of life. Ammonium transport is mediated by the ubiquitous Amt/Mep/Rh transporters that includes the human Rhesus factors. Here, using a combination of electrophysiology, yeast functional complementation and extended molecular dynamics simulations, we reveal a unique two-lane pathway for electrogenic NH4+ transport in two archetypal members of the family, the transporters AmtB from Escherichia coli and Rh50 from Nitrosomonas europaea. The pathway underpins a mechanism by which charged H+ and neutral NH3 are carried separately across the membrane after NH4+ deprotonation. This mechanism defines a new principle of achieving transport selectivity against competing ions in a biological transport process.