TY  - JOUR
AU  - Chiariello, Maria Gabriella
AU  - Alfonso-Prieto, Mercedes
AU  - Ippoliti, Emiliano
AU  - Fahlke, Christoph
AU  - Carloni, Paolo
TI  - Mechanisms Underlying Proton Release in CLC-type F – /H + Antiporters
JO  - The journal of physical chemistry letters
VL  - 12
IS  - 18
SN  - 1948-7185
CY  - Washington, DC
PB  - ACS
M1  - FZJ-2021-02425
SP  - 4415 - 4420
PY  - 2021
N1  - Funded by Deutsche Forschungsgemeinschaft via the Research Unit FOR2518 “Functional Dynamics of Ion Channels and Transporters − DynIon”, project P6.
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:33950673
UR  - <Go to ISI:>//WOS:000651787900012
DO  - DOI:10.1021/acs.jpclett.1c00361
UR  - https://juser.fz-juelich.de/record/892901
ER  -