%0 Journal Article
%A Chiariello, Maria Gabriella
%A Alfonso-Prieto, Mercedes
%A Ippoliti, Emiliano
%A Fahlke, Christoph
%A Carloni, Paolo
%T Mechanisms Underlying Proton Release in CLC-type F – /H + Antiporters
%J The journal of physical chemistry letters
%V 12
%N 18
%@ 1948-7185
%C Washington, DC
%I ACS
%M FZJ-2021-02425
%P 4415 - 4420
%D 2021
%Z Funded by Deutsche Forschungsgemeinschaft via the Research Unit FOR2518 “Functional Dynamics of Ion Channels and Transporters − DynIon”, project P6.
%X The CLC family of anion channels and transporters includes Cl–/H+ exchangers (blocked by F–) and F–/H+ exchangers (or CLCFs). CLCFs contain a glutamate (E318) in the central anion-binding site that is absent in CLC Cl–/H+ exchangers. The X-ray structure of the protein from Enterococcus casseliflavus (CLCF-eca) shows that E318 tightly binds to F– when the gating glutamate (E118; highly conserved in the CLC family) faces the extracellular medium. Here, we use classical and DFT-based QM/MM metadynamics simulations to investigate proton transfer and release by CLCF-eca. After up to down movement of protonated E118, both glutamates combine with F– to form a triad, from which protons and F– anions are released as HF. Our results illustrate how glutamate insertion into the central anion-binding site of CLCF-eca permits the release of H+ to the cytosol as HF, thus enabling a net 1:1 F–/H+ stoichiometry.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:33950673
%U <Go to ISI:>//WOS:000651787900012
%R 10.1021/acs.jpclett.1c00361
%U https://juser.fz-juelich.de/record/892901