4JOR

CFTR Associated Ligand (CAL) PDZ domain bound to HPV18 E6 oncoprotein C-terminal peptide (RLQRRRETQV)

Summary for 4JOR

• Entry DOI: 10.2210/pdb4jor/pdb
• Related: 4JOE 4JOF 4JOG 4JOH 4JOJ 4JOK 4JOP
• Descriptor: Golgi-associated PDZ and coiled-coil motif-containing protein, Protein E6, GLYCEROL, ... (4 entities in total)
• Functional Keywords: pdz, cftr associated ligand, cal, pist, fig, human papillomavirus type 18, hpv18, e6 oncoprotein, peptide binding protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 21582.74

Authors

Amacher, J.F.,Madden, D.R. (deposition date: 2013-03-18, release date: 2014-01-22, Last modification date: 2023-09-20)

Primary citation

Amacher, J.F.,Cushing, P.R.,Brooks, L.,Boisguerin, P.,Madden, D.R.
Stereochemical Preferences Modulate Affinity and Selectivity among Five PDZ Domains that Bind CFTR: Comparative Structural and Sequence Analyses.
Structure, 22:82-93, 2014

PubMed Abstract: PDZ domain interactions are involved in signaling and trafficking pathways that coordinate crucial cellular processes. Alignment-based PDZ binding motifs identify the few most favorable residues at certain positions along the peptide backbone. However, sequences that bind the CAL (CFTR-associated ligand) PDZ domain reveal only a degenerate motif that overpredicts the true number of high-affinity interactors. Here, we combine extended peptide-array motif analysis with biochemical techniques to show that non-motif "modulator" residues influence CAL binding. The crystallographic structures of 13 CAL:peptide complexes reveal defined, but accommodating stereochemical environments at non-motif positions, which are reflected in modulator preferences uncovered by multisequence substitutional arrays. These preferences facilitate the identification of high-affinity CAL binding sequences and differentially affect CAL and NHERF PDZ binding. As a result, they also help determine the specificity of a PDZ domain network that regulates the trafficking of CFTR at the apical membrane.

PubMed: 24210758
DOI: 10.1016/j.str.2013.09.019

Experimental method

X-RAY DIFFRACTION (1.34 Å)