TY  - CONF
AU  - Chiariello, Gabriella
AU  - Alfonso-Prieto, Mercedes
AU  - Ippoliti, Emiliano
TI  - Molecular Origin of the Unusual Proton/Fluoride Stoichiometry of CLC-Type Fluoride Transporters
VL  - 450
CY  - Jülich
PB  - Forschungszentrum Jülich GmbH Zentralbibliothek, Verlag
M1  - FZJ-2022-04944
SN  - 978-3-95806-646-5
T2  - Publication Series of the John von Neumann Institute for Computing (NIC) NIC Series 51
SP  - 189-198
PY  - 2022
AB  - Fluoride (F–) is present in natural water sources at concentrations that are toxic to unicellular organisms. Thus, prokaryotes have evolved export transporters for this anion to ensure their survival. One such group of fluoride transporters are the F−/H+ exchangers belonging to the CLC family (CLCF s). The X-ray structure of the Enterococcus casseliflavus CLCF (CLCF -eca) contains a glutamate (E318) in the central anion-binding site, which is absent in the conventional CLCs and has been suggested as one of the determinants enabling fluoride transport. Here we use classical and subnanosecond QM/MM metadynamics simulations to investigate the molecular basis of the 1:1 proton:fluoride stoichiometry in CLCF -eca. The proton release mechanism relies on the formation of the E318-F-E118 triad, stabilised by a complex H-bond network in which both glutamates interact with F−. The interplay between the two glutamates enables protonation of fluoride and proton release as HF into the intracellular solution. Our results demonstrate how glutamate insertion into the central anion-binding site of CLCF-eca permits F− release coupled to H+ inward movement, resulting in effective and selective F− transport.
T2  - NIC Symposium
CY  - 29 Sep 2022 - 30 Sep 2022, Jülich (Germany)
Y2  - 29 Sep 2022 - 30 Sep 2022
M2  - Jülich, Germany
LB  - PUB:(DE-HGF)8 ; PUB:(DE-HGF)7
UR  - https://juser.fz-juelich.de/record/911690
ER  -