Referenced in: none

Automatically associated channels: ClC1 , ClC4

Title: Conservation of chloride channel structure revealed by an inhibitor binding site in ClC-1.

Authors: Raúl Estévez, Björn C Schroeder, Alessio Accardi, Thomas J Jentsch, Michael Pusch

Journal, date & volume: Neuron, 2003 Apr 10 , 38, 47-59

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/12691663

Abstract
Crystal structures of bacterial CLC proteins were solved recently, but it is unclear to which level of detail they can be extrapolated to mammalian chloride channels. Exploiting the difference in inhibition by 9-anthracene carboxylic acid (9-AC) between ClC-0, -1, and -2, we identified a serine between helices O and P as crucial for 9-AC binding. Mutagenesis based on the crystal structure identified further residues affecting inhibitor binding. They surround a partially hydrophobic pocket close to the chloride binding site that is accessible from the cytoplasm, consistent with the observed intracellular block by 9-AC. Mutations in presumably Cl--coordinating residues yield additional insights into the structure and function of ClC-1. Our work shows that the structure of bacterial CLCs can be extrapolated with fidelity to mammalian Cl- channels.