CFTR Chloride Channel Regulation by an Interdomain Interaction

• DOI: 10.1126/science.286.5439.544
• Publication Date: 2002-07-27T09:42:20Z
• Authors: Anjaparavanda P. ...; Estelle Cormet-Bo...; Jian Fu; Matteo Villain; J. Edwin Blalock; Michael W. Quick; Kevin L. Kirk
• Keywords: Chloride channel; Protein kinase domain

The cystic fibrosis gene encodes a chloride channel, CFTR (cystic transmembrane conductance regulator), that regulates salt and water transport across epithelial tissues. Phosphorylation of the cytoplasmic regulatory (R) domain by protein kinase A activates an unknown mechanism. amino-terminal tail was found to control A–dependent channel gating through physical interaction with R domain. This activity mapped cluster acidic residues in NH 2 -terminal tail; mutating these proportionately inhibited binding function. appears be governed interdomain involving tail, which is potential target for physiologic pharmacologic modulators this ion channel.