ABCC7/CFTR

Abstract

The cystic fibrosis transmembrane conductance regulator (CFTR), also known as ABCC7, is an unusual member of the ATP-binding cassette family in that it is an ion channel rather than a transporter. Here, ATP binding is thought to initiate channel opening, with hydrolysis of the nucleotide being associated with channel closure. Loss of CFTR function through mutation leads to the life-threatening and -shortening condition known as cystic fibrosis. Recently, the importance of external factors affecting CFTR function has also been reported. In this chapter I have focussed on the basic structural biology and biochemistry of the protein but have also attempted to link this knowledge with the understanding of the disease. I have employed a bottom-up approach, starting with what can be learned from the primary structure of the protein, leading on to an examination of the secondary and tertiary structure of CFTR. The mapping of common CF-causing missense mutations within the CFTR 3D structure will also be addressed here. Lastly, the chapter finishes with some discussion of the prospects for future research on CFTR and how data for the channel function of CFTR can inform the ATP-binding cassette field of study in general.