Crystallization and Preliminary Diffraction Analysis of the CAL PDZ Domain in Complex with a Selective Peptide Inhibitor

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Publication Date


Publication Title

Acta Crystallographica. Section F - Structural Biology and Crystallization Communications


Geisel School of Medicine


Cystic fibrosis (CF) is associated with loss-of-function mutations in the CF transmembrane conductance regulator (CFTR), which regulates epithelial fluid and ion homeostasis. The CFTR cytoplasmic C-terminus interacts with a number of PDZ (PSD-95/Dlg/ZO-1) proteins that modulate its intracellular trafficking and chloride-channel activity. Among these, the CFTR-associated ligand (CAL) has a negative effect on apical-membrane expression levels of the most common disease-associated mutant ΔF508-CFT, making CAL a candidate target for the treatment of CF. A selective peptide inhibitor of the CAL PDZ domain (iCAL36) has recently been developed and shown to stabilize apical expression of F508-CFTR, enhancing net chloride-channel activity, both alone and in combination with the folding corrector corr-4a. As a basis for structural studies of the CAL-iCAL36 interaction, a purification protocol has been developed that increases the oligomeric homogeneity of the protein. Here, the co­crystallization of the complex in space group P212121, with unit-cell parameters a = 35.9, b = 47.7, c = 97.3 Å, is reported. The crystals diffracted to 1.4 Å resolution. Based on the calculated Matthews coefficient (1.96 Å3 Da-1), it appears that the asymmetric unit contains two complexes.



Original Citation

Amacher JF, Cushing PR, Weiner JA, Madden DR. Crystallization and preliminary diffraction analysis of the CAL PDZ domain in complex with a selective peptide inhibitor. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2011 May 1;67(Pt 5):600-3. doi: 10.1107/S1744309111009985. Epub 2011 Apr 28. PMID: 21543871; PMCID: PMC3087650.