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@INPROCEEDINGS{Chiariello:911690,
author = {Chiariello, Gabriella and Alfonso-Prieto, Mercedes and
Ippoliti, Emiliano},
title = {{M}olecular {O}rigin of the {U}nusual {P}roton/{F}luoride
{S}toichiometry of {CLC}-{T}ype {F}luoride {T}ransporters},
volume = {450},
address = {Jülich},
publisher = {Forschungszentrum Jülich GmbH Zentralbibliothek, Verlag},
reportid = {FZJ-2022-04944},
isbn = {978-3-95806-646-5},
series = {Publication Series of the John von Neumann Institute for
Computing (NIC) NIC Series 51},
pages = {189-198},
year = {2022},
comment = {NIC Symposium 2022 Proceedings},
booktitle = {NIC Symposium 2022 Proceedings},
abstract = {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.},
month = {Sep},
date = {2022-09-29},
organization = {NIC Symposium, Jülich (Germany), 29
Sep 2022 - 30 Sep 2022},
cin = {IAS-5 / INM-9},
cid = {I:(DE-Juel1)IAS-5-20120330 / I:(DE-Juel1)INM-9-20140121},
pnm = {5241 - Molecular Information Processing in Cellular Systems
(POF4-524)},
pid = {G:(DE-HGF)POF4-5241},
typ = {PUB:(DE-HGF)8 / PUB:(DE-HGF)7},
url = {https://juser.fz-juelich.de/record/911690},
}