CryoEM structures of the human CLC-2 voltage gated chloride channel reveal a ball and chain gating mechanism.

ABSTRACT: CLC-2 is a voltage-gated chloride channel that contributes to electrical excitability and ion homeostasis in many different mammalian tissues and cell types. Among the nine mammalian CLC homologs, CLC-2 is uniquely activated by hyperpolarization, rather than depolarization, of the plasma membrane. The molecular basis for the divergence in polarity of voltage gating mechanisms among closely related CLC homologs has been a long-standing mystery, in part because few CLC channel structures are available, and those that exist exhibit high conformational similarity. Here, we report cryoEM structures of human CLC-2 at 2.46 - 2.76 Å, in the presence and absence of the potent and selective inhibitor AK-42. AK-42 binds within the extracellular entryway of the Cl^--permeation pathway, occup

SUBMITTER: Xu M 

PROVIDER: S-EPMC10462068 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature