Both chloride-binding sites are required for KCC2-mediated transport.

ABSTRACT: The K⁺-Cl^- cotransporter 2 (KCC2) plays an important role in inhibitory neurotransmission, and its impairment is associated with neurological and psychiatric disorders, including epilepsy, schizophrenia, and autism. Although KCCs transport K⁺ and Cl^- in a 1:1 stoichiometry, two Cl^- coordination sites were indicated via cryo-EM. In a comprehensive analysis, we analyzed the consequences of point mutations of residues coordinating Cl^- in Cl₁ and Cl₂. Individual mutations of residues in Cl₁ and Cl₂ reduce or abolish KCC2^WT function, indicating a crucial role of both Cl^- coordination sites for KCC2 function. Structural changes in the extracellular loop 2 by inserti

SUBMITTER: Becker L 

PROVIDER: S-EPMC10518353 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature