A two-lane mechanism for selective biological ammonium transport

TY - JOUR

T1 - A two-lane mechanism for selective biological ammonium transport

AU - Williamson, Gordon

AU - Tamburrino, Giulia

AU - Bizior, Adriana

AU - Boeckstaens, Mélanie

AU - Dias Mirandela, Gaëtan

AU - Bage, Marcus

AU - Pisliakov, Andrei

AU - Ives, Callum M.

AU - Terras, Eilidh

AU - Hoskisson, Paul A.

AU - Marini, Anna-Maria

AU - Zachariae, Ulrich

AU - Javelle, Arnaud

N1 - Funding Information: Special thanks to Prof. Iain Hunter (Strathclyde Institute of Pharmacy and Biomedical Sciences) for invaluable discussions and help during this project. We also thank Pascale Van Vooren for technical support and Thomas P. Jahn for sharing the triple-mep? trk,1,2? yeast strain. Publisher Copyright: © 2020, eLife Sciences Publications Ltd. All rights reserved. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/7

Y1 - 2020/7

N2 - 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.

AB - 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.

KW - E. coli

KW - SSME

KW - Saccharomyces cerevisiae

KW - ammonium transporter

KW - biochemistry

KW - chemical biology

KW - nitrosomonas europaea

KW - rhesus protein

KW - transport selectivity

UR - https://www.scopus.com/pages/publications/85090068799

U2 - 10.7554/eLife.57183

DO - 10.7554/eLife.57183

M3 - Article

C2 - 32662768

SN - 2050-084X

VL - 9

JO - eLife

JF - eLife

M1 - e57183

ER -