Functional dissection of the R domain of cystic fibrosis transmembrane conductance regulator

Exogenously expressed unphosphorylated sub-domains of the R domain block CFTR Cl − channels in the planar lipid bilayer, though the block differs from block with full length R domain. Full length R domain peptide (aa 588–855) blocks CFTR Cl − channels quickly, completely and permanently [1]. Two sub-domains, RD1RD2 (aa 588–805) and RD2TM (aa 672–855), also inhibit CFTR Cl − channels, but the block takes longer to effect and is not complete. Shorter sequences, RD1 (aa 588–746) and RD2 (aa 672–805), fail to effect any block. These data suggest that either the amino-terminal or carboxy-terminal portions of the R domain protein or its stabilized secondary structure are critical to functional regulation.