Structural basis of pH-dependent activation in a CLC transporter.

ABSTRACT: CLCs are dimeric chloride channels and anion/proton exchangers that regulate processes such as muscle contraction and endo-lysosome acidification. Common gating controls their activity; its closure simultaneously silences both protomers, and its opening allows them to independently transport ions. Mutations affecting common gating in human CLCs cause dominant genetic disorders. The structural rearrangements underlying common gating are unknown. Here, using single-particle cryo-electron microscopy, we show that the prototypical Escherichia coli CLC-ec1 undergoes large-scale rearrangements in activating conditions. The slow, pH-dependent remodeling of the dimer interface leads to the concerted opening of the intracellular H⁺ pathways and is required for transport. The more frequen

SUBMITTER: Fortea E 

PROVIDER: S-EPMC11262703 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature