Conformational changes in CIC chloride transporters

National Institute Of Neurological Disorders And Stroke

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Abstract

This project continued studying conformational changes in ClC-type chloride channel proteins. The ClC family of chloride-conducting ion channels is involved in a host of biological processes; these channels maintain the resting membrane potential in skeletal muscle, modulate excitability in central neurons, and are involved in the homeostasis of pH in a variety of intracellular compartments. Despite their physiological importance, the mechanisms by which these channels function are poorly understood. We are attempting to understand the functional properties of these proteins by examining several family members, including both eukaryotic and prokaryotic homologs. Our current focus in this area is to observe the flux due to a single ClC transporter in a single proteoliposome. We are doing this using single molecule methods in collaboration with Dimitrios Stamou at the University of Copenhagen. Toward this end we have developed a robust bulk assay of chloride-coupled proton transport, and then subjected individual liposomes to similar conditions. In this circumstances, we observe robust acidification in single liposomes. We are currently optimizing these assays and trying to improve their robustness.