Referenced in: none

Automatically associated channels: ClC4

Title: Conformational changes required for H(+)/Cl(-) exchange mediated by a CLC transporter.

Authors: Daniel Basilio, Kristin Noack, Alessandra Picollo, Alessio Accardi

Journal, date & volume: Nat. Struct. Mol. Biol., 2014 May , 21, 456-63

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24747941

Abstract
CLC-type exchangers mediate transmembrane Cl(-) transport. Mutations altering their gating properties cause numerous genetic disorders. However, their transport mechanism remains poorly understood. In conventional models, two gates alternatively expose substrates to the intra- or extracellular solutions. A glutamate was identified as the only gate in the CLCs, suggesting that CLCs function by a nonconventional mechanism. Here we show that transport in CLC-ec1, a prokaryotic homolog, is inhibited by cross-links constraining movement of helix O far from the transport pathway. Cross-linked CLC-ec1 adopts a wild-type-like structure, indicating stabilization of a native conformation. Movements of helix O are transduced to the ion pathway via a direct contact between its C terminus and a tyrosine that is a constitutive element of the second gate of CLC transporters. Therefore, the CLC exchangers have two gates that are coupled through conformational rearrangements outside the ion pathway.