Arnaud Billet, Jean-Paul Mornon, Mathilde Jollivet, Pierre Lehn, Isabelle Callebaut, Frédéric Becq
BACKGROUND: CFTR is the only ABC transporter functioning as a chloride (Cl(-)) channel. We studied molecular determinants, which might distinguish CFTR from standard ABC transporters, and focused on the interface formed by the intracellular loops from the membrane spanning domains. METHODS: Residues from ICL2 and ICL4 in close proximity were targeted, and their involvement in the functioning of CFTR was studied by whole cell patch clamp recording. RESULTS: We identified 2 pairs of amino acids, at the extremity of the bundle formed by the four intracellular loops, whose mutation i) decreases the Cl(-) current of CFTR (couple E267-K1060) or ii) increases it with a change of the electrophysiological signature (couple S263-V1056)...
December 2013: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society