Chloride Intracellular Channels (CLICs) are a family of proteins that are somewhat unique because they exist as both a globular, soluble form as well as an oligomeric form that is capable of traversing the membrane. As CLICs can autonomously switch between these two different forms reversibly they belong to a class of proteins recently coined ‘metamorphic’ [1]. CLIC proteins are highly conserved in nature and have a wide cellular distribution suggesting they play a vital cellular role. Electrophysiological studies have shown that the membrane-inserted form of CLICs can function as ion channels, however, their main physiological function is not very well understood.

The soluble form of several CLIC family members have been solved by X-ray crystallography. However, due to the metamorphic nature of CLICs, efforts in solving the membrane-inserted structures have so far been unsuccessful. In this study, Fluorescence Resonance Energy Transfer spectroscopy has been used to measure distances between the CLIC1 protein and the lipid bilayer. The established assay can also be used to test different environmental parameters that may promote insertion of CLIC1 into the bilayer. Transmission Electron Microscopy has also been used to image the CLIC1 oligomeric structure in the presence of lipids. The outcome of this research is to construct a model for how CLIC1 sits in the lipid bilayer and to gain some insight into the oligomeric ion channel structure.