A two-lane mechanism for selective biological ammonium transport

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. A particular controversy has existed around the mechanism of ammonium exchange by the ubiquitous Amt/Mep/Rh transporter family, an essential process in all kingdoms of life. Here, using a combination of SSME 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 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.