4K76

CFTR Associated Ligand (CAL) PDZ domain bound to peptide iCAL36-TRL (ANSRWPTTRL)

4K76 の概要

• エントリーDOI: 10.2210/pdb4k76/pdb
• 関連するPDBエントリー: 4JOP 4JOR 4K6Y 4K72 4K75 4K78
• 分子名称: Golgi-associated PDZ and coiled-coil motif-containing protein, iCAL36-TRL peptide, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: pdz domain, cal, pist, fig, pdz-peptide complex, cftr associated ligand, cftr, peptide binding protein-protein binding complex, peptide binding protein/protein binding
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: Q9HD26
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 42320.39

構造登録者

Amacher, J.F.,Madden, D.R. (登録日: 2013-04-16, 公開日: 2014-02-26, 最終更新日: 2023-09-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.75 Å)