Elucidating the Membrane Insertion Mechanism of Chloride Intracellular Channel Proteins

Chloride Intracellular Channels (CLICs) are a family of 6 proteins that have in common a C-terminal CLIC module and chloride-selective ion channel activity. CLIC1 is a 241 amino-acid protein involved in the regulation of the cell cycle, in particular it is overexpressed in a number of cancer cells. However, to date little information exists as to its structure and the factors that influence its insertion into membranes. Here we propose to supplement previous neutron reflectivity experiments with data collected using a deuterated form of the CLIC-1 protein. This will be used in combination with a broad range of ongoing biophysical characterisation to establish the mechanism of CLIC1 chloride channel insertion as a function of membrane charge. This will be an initial step to understand how CLIC1 functions in tumour cells and will allow specific treatments to be designed to interrupt it.