The ATP-binding cassette (ABC) superfamily proteins are important functional transporters in both prokaryotes and eukaryotes, playing the primary roles in mediating the entry and exit of a variety of molecules, which is essential for growth and regulation. Increasing evidence has shown that the native forms of these membrane-bound proteins are highly organized macromolecular complexes where the molecular composition and functional stoichiometry confer the native biology of these proteins and are dynamically regulated.The long-term objective of the proposed research is aimed at investigating the molecular organization and function of ABC transporting by focusing on cystic fibrosis transmembrane conductance regulator (CFTR). In particular, we will focus on biochemical and functional interactions between the CFTR and its associated proteins. The proposed experiments in this application focus on a group of four previously unknown CFTR-Associated proteins (CAPs) that have been purified on the basis of high affinity association with the CFTR protein. The genes encoding these four CAPs have been isolated in our laboratory. The proposed experiments are designed to address their potential molecular and functional roles in the CFTR activities. Through a combination of proposed biochemical, cellular, molecular, and electrophysiological experiments, we wish to obtain important information about the mechanism by which CAPs interact with CFTR as well as the potential functional roles of CAPs in modulation of the CFTR activity. Cystic Fibrosis (CF) is an autosomal recessive disorder caused primarily by mutations of a membrane channel protein known as cystic fibrosis transmembrane conductance regulator (CFTR). The mutations found in CF patients cause changes of both channel activity and subcellular location of the CFTR protein. Interactions between CFTR and other structural and regulatory proteins are essential for its proper function in human. Thus, the knowledge about these various interactions is essential for the full understanding of human diseases caused by the mutated CFTR
