A two-lane mechanism for selective biological ammonium transport
Gordon Williamson, Giulia Tamburrino, Adriana Bizior, Mélanie Boeckstaens, Gaëtan Dias Mirandela, Marcus Bage, Andrei V. Pisliakov, Callum M. Ives, Eilidh Terras, Paul A. Hoskisson, Anna Maria Marini, Ulrich Zachariae, Arnaud Javelle
Abstract
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 NH 4 + 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 NH 3 are carried separately across the membrane after NH 4 + deprotonation. This mechanism defines a new principle of achieving transport selectivity against competing ions in a biological transport process.