Structure-function study of the CFTR (ABCC7) chloride channel

ABC transporters are a family of protein which play numerous important roles in organism physiology, from bacteria to human. They translocate a wide variety of molecules such as sugars, vitamins and even small proteins in different compartment of the cell or outside of cells. The 48 human ABC proteins are mostly exporters involved in secretions , drug detoxification, and the immune system. Structural studies have been instrumental in discovering the 3D structure of bacterial ABC proteins, providing numerous information on how they work. Unfortunately, for more complex ABC proteins, like the human ones, which are involved in many important physiological functions, it is not possible to purify them and obtain a precise 3D structure by crystallisation. Most of their characteristics and functional properties are thus determined by comparison with bacterial ABC transporters. As a result, current models need to be further tested and evaluated by functional and physiologically relevant studies, such as those we propose in our research program. We study the CFTR protein, an important human ABC transporter that plays a crucial role in the regulation of salts and water movement across the epithelial cells of the lungs, pancreas, liver, intestine and reproductive tract. By analysis of multiple physical and functional aspect of this protein our aim is to obtain critically missing information of the transport mechanism of the CFTR protein that can be applied to other related ABC transporters which are anticipated to function similarly.