Divergent Cl; -; and H; +; pathways underlie transport coupling and gating in CLC exchangers and channels

Leisle, Lilia and Xu, Yanyan and Fortea, Eva and Lee, Sangyun and Galpin, Jason D. and Vien, Malvin and Ahern, Christopher A. and Accardi, Alessio and Bernèche, Simon. (2020) Divergent Cl; -; and H; +; pathways underlie transport coupling and gating in CLC exchangers and channels. eLife, 9. e51224.

PDF - Published Version
Available under License CC BY (Attribution).


Official URL: https://edoc.unibas.ch/78960/

Downloads: Statistics Overview


The CLC family comprises H; +; -coupled exchangers and Cl; -; channels, and mutations causing their dysfunction lead to genetic disorders. The CLC exchangers, unlike canonical 'ping-pong' antiporters, simultaneously bind and translocate substrates through partially congruent pathways. How ions of opposite charge bypass each other while moving through a shared pathway remains unknown. Here, we use MD simulations, biochemical and electrophysiological measurements to identify two conserved phenylalanine residues that form an aromatic pathway whose dynamic rearrangements enable H; +; movement outside the Cl; -; pore. These residues are important for H; +; transport and voltage-dependent gating in the CLC exchangers. The aromatic pathway residues are evolutionarily conserved in CLC channels where their electrostatic properties and conformational flexibility determine gating. We propose that Cl; -; and H; +; move through physically distinct and evolutionarily conserved routes through the CLC channels and transporters and suggest a unifying mechanism that describes the gating mechanism of both CLC subtypes.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Computational Biophysics (Bernèche)
UniBasel Contributors:Bernèche, Simon and Xu, Yanyan
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:eLife Sciences Publications
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
edoc DOI:
Last Modified:26 Jan 2022 16:07
Deposited On:26 Jan 2022 16:07

Repository Staff Only: item control page