Journal Article

FZJ-2021-02425

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Mechanisms Underlying Proton Release in CLC-type F – /H + Antiporters

Chiariello, M. G. (Corresponding author)FZJ* ; Alfonso-Prieto, M.FZJ* ; Ippoliti, E.FZJ* ; Fahlke, C. (Corresponding author)FZJ* ; Carloni, P. (Corresponding author)FZJ*

2021
ACS Washington, DC

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Please use a persistent id in citations: http://hdl.handle.net/2128/28738  doi:10.1021/acs.jpclett.1c00361

Abstract: 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.

Note: Funded by Deutsche Forschungsgemeinschaft via the Research Unit FOR2518 “Functional Dynamics of Ion Channels and Transporters − DynIon”, project P6.

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Contributing Institute(s):

1. Computational Biomedicine (IAS-5)
2. Computational Biomedicine (INM-9)
3. Molekular- und Zellphysiologie (IBI-1)
4. Jara-Institut Quantum Information (INM-11)
5. JARA - HPC (JARA-HPC)

Research Program(s):

1. 524 - Molecular and Cellular Information Processing (POF4-524) (POF4-524)
2. DFG project 291198853 - FOR 2518: Funktionale Dynamik von Ionenkanälen und Transportern - DynIon - (291198853)

Appears in the scientific report 2021

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Database coverage:
; ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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