title: CFTR: effect of ICL2 and ICL4 amino acids in close spatial proximity on the current properties of the channel.
abstract: 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).
  
  
  CONCLUSIONS
  These results highlight the critical role of these ICL residues in the assembly of the different domains and/or in the Cl(-) permeation pathway of CFTR.
authors.affiliation: Institut de Physiologie et Biologie Cellulaires, Université de Poitiers, CNRS, Poitiers, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Billet
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Mornon
authors.forename: Mathilde
authors.initials: M
authors.lastname: Jollivet
authors.forename: Pierre
authors.initials: P
authors.lastname: Lehn
authors.forename: Isabelle
authors.initials: I
authors.lastname: Callebaut
authors.forename: Frédéric
authors.initials: F
authors.lastname: Becq
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D020816:Amino Acid Motifs; D015153:Blotting, Western; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008958:Models, Molecular; D018408:Patch-Clamp Techniques; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D018528:ATP-Binding Cassette Transporters; C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator
keywords: ABC transporter; CFTR; Channel gating; ICL; Structure-function