RT Journal Article
SR Electronic
T1 A mechanistic switch from selective transporter to an ion channel impairs the filamentation signalling capability of ammonium transceptors in yeast
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.08.25.457613
DO 10.1101/2021.08.25.457613
A1 Gordon Williamson
A1 Ana Sofia Brito
A1 Adriana Bizior
A1 Giulia Tamburrino
A1 Gaëtan Dias Mirandela
A1 Thomas Harris
A1 Paul A. Hoskisson
A1 Ulrich Zachariae
A1 Anna Maria Marini
A1 Mélanie Boeckstaens
A1 Arnaud Javelle
YR 2021
UL http://biorxiv.org/content/early/2021/08/25/2021.08.25.457613.abstract
AB Ammonium translocation through biological membranes by the ubiquitous Amt-Mep-Rh family of transporters plays a key role in all domains of life. Two highly conserved histidine residues protrude into the lumen of these transporters, forming the family’s characteristic Twin-His motif. It has been hypothesized that the motif is essential to confer the selectivity of the transport mechanism. Here, using a combination of in vitro electrophysiology, in vivo yeast functional complementation and in silico molecular dynamics simulations, we demonstrate that variations in the Twin-His motif trigger a mechanistic switch between a specific transporter, depending on ammonium deprotonation, to an unspecific ion channel activity. We therefore propose that there is no selective filter that governs the specificity in Amt-Mep transporters but the inherent mechanism of translocation, dependent on the fragmentation of the substrate, ensures the high specificity of the translocation. We further show that both mechanisms coexist in fungal Mep2 Twin-His variants, disrupting the transceptor function and so inhibiting the filamentation process. These data strongly support a transport mechanism-mediated signalling process in the long-standing debate on the sensory function of Mep2-like transporters.Competing Interest StatementThe authors have declared no competing interest.