Fig. 2.

a. Depictions of post-synaptic density 95/discs large/zona occludens 1 (PDZ) domain organization and structure. Top Linear cartoon representation showing the predicted secondary structural elements above the relevant sequence (amino acid residues 309–393) from an archetypal PDZ domain, rat PSD-95 PDZ-3. Blue arrows β sheets, purple rectangles α helices. Residues shown in boldface contact the peptide binding partner. Note that the binding loop rests in the region intervening between βA and βB. Bottom Three-dimensional structure of the PDZ-3 of postsynaptic density protein-95 (PSD-95) showing the interacting peptide (orange arrow) wedged between the groove formed by the βB sheet and the αB helix; the carboxylate binding loop hovers above. This image is modified from Doyle et al. (1996), with permission from Elsevier. b Cartoon showing hypothesized apical macromolecular signaling complexes promoted by PDZ protein-facilitated interactions between the CFTR and SLC26 transporters. PDZ domain binding motif of SLC26A3, TKF, is shown in this figure; the counterpart for SLC26A6 is TRL. For CFTR, the motif is TRL as shown. This motif is lacking in SLC26A4, but the potential for regulation by sulfate transporter and anti-sigma factor antagonist (STAS) domain interactions with the R domain of CFTR is preserved