Architecture and functional properties of the CFTR channel pore

Cell Mol Life Sci. 2017 Jan;74(1):67-83. doi: 10.1007/s00018-016-2389-5. Epub 2016 Oct 3.

Abstract

The main function of the cystic fibrosis transmembrane conductance regulator (CFTR) is as an ion channel for the movement of small anions across epithelial cell membranes. As an ion channel, CFTR must form a continuous pathway across the cell membrane-referred to as the channel pore-for the rapid electrodiffusional movement of ions. This review summarizes our current understanding of the architecture of the channel pore, as defined by electrophysiological analysis and molecular modeling studies. This includes consideration of the characteristic functional properties of the pore, definition of the overall shape of the entire extent of the pore, and discussion of how the molecular structure of distinct regions of the pore might control different facets of pore function. Comparisons are drawn with closely related proteins that are not ion channels, and also with structurally unrelated proteins with anion channel function. A simple model of pore function is also described.

Keywords: ABC protein; CFTR; Channel pore; Chloride channel; Cystic fibrosis; Ion selectivity.

Publication types

  • Review

MeSH terms

  • Animals
  • Anions / metabolism
  • Cell Membrane / metabolism
  • Cystic Fibrosis / metabolism
  • Cystic Fibrosis Transmembrane Conductance Regulator / chemistry*
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism*
  • Cytoplasm / metabolism
  • Humans
  • Models, Molecular
  • Protein Conformation

Substances

  • Anions
  • Cystic Fibrosis Transmembrane Conductance Regulator