Structure of a Eukaryotic CLC Transporter Defines an Intermediate State in the Transport Cycle

Abstract

Controlling Chloride Channels: The CLC proteins are a large family of channels and transporters that transfer chloride ions across cell membranes. While structures of two prokaryotic CLCs have been determined, these do not include the cytoplasmic regulatory domains found in eukaryotic transporters, and the structures do not reveal the mechanism of Cl ⁻ /H ⁺ –coupled transport. L. Feng et al. (p. 635 , published online 30 September; see the Perspective by Mindell ) describe the structure of a eukaryotic CLC protein and found that the regulatory domains interacted closely with the transmembrane domain so that conformational changes are transmitted to the ion pathway. A gating glutamate in the eukaryote transporter is in a different conformation to prokaryotic structures, explaining the 2:1 stoichiometry of Cl ⁻ /H ⁺ exchange in eukaryotes.