2LOB

PDZ Domain of CAL (Cystic Fibrosis Transmembrane Regulator-Associated Ligand)

Summary for 2LOB

• Entry DOI: 10.2210/pdb2lob/pdb
• NMR Information: BMRB: 18205
• Descriptor: Golgi-associated PDZ and coiled-coil motif-containing protein, Cystic fibrosis transmembrane conductance regulator (2 entities in total)
• Functional Keywords: structural protein-hydrolase complex, peptide binding protein
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: Q9HD26; Early endosome membrane; Multi-pass membrane protein: P13569
• Total number of polymer chains: 2
• Total formula weight: 13518.19

Authors

Piserchio, A.,Fellows, A.,Madden, D.R.,Mierke, D.F. (deposition date: 2012-01-20, release date: 2012-06-13, Last modification date: 2024-05-01)

Primary citation

Piserchio, A.,Fellows, A.,Madden, D.R.,Mierke, D.F.
Association of the cystic fibrosis transmembrane regulator with CAL: structural features and molecular dynamics.
Biochemistry, 44:16158-, 2005

PubMed Abstract: The association of the cystic fibrosis transmembrane regulator (CFTR) with two PDZ-containing molecular scaffolds (CAL and EBP50) plays an important role in CFTR trafficking and membrane maintenance. The CFTR-molecular scaffold interaction is mediated by the association of the C-terminus of the transmembrane regulator with the PDZ domains. Here, we characterize the structure and dynamics of the PDZ of CAL and the complex formed with CFTR employing high-resolution NMR. On the basis of NMR relaxation data, the alpha2 helix as well as the beta2-beta3 loop of CAL PDZ domain undergoes rapid dynamics. Molecular dynamics simulations suggest a concerted motion between the alpha2 helix and the beta1-beta2 and beta2-beta3 loops, elements which define the binding pocket, suggesting that dynamics may play a role in PDZ-ligand specificity. The C-terminus of CFTR binds to CAL with the final four residues (-D(-)(3)-T-R-L(0)) within the canonical PDZ-binding motif, between the beta2 strand and the alpha2 helix. The R(-)(1) and D(-)(3) side chains make a number of contacts with the PDZ domain; many of these interactions differ from those in the CFTR-EBP50 complex, suggesting sites that can be targeted in the development of PDZ-selective inhibitors that may help modulate CFTR function.

PubMed: 16331976

Experimental method

SOLUTION NMR