8S6A

X-ray structure of Dishevelled 3 PDZ domain in a complex with a class III peptide ligand

8S6A の概要

• エントリーDOI: 10.2210/pdb8s6a/pdb
• 分子名称: Segment polarity protein dishevelled homolog DVL-3, C8 peptide (3 entities in total)
• 機能のキーワード: dishevelled, wnt signalling, signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 24950.55

構造登録者

Komarek, J.,Barinka, C. (登録日: 2024-02-26, 公開日: 2025-03-12, 最終更新日: 2025-08-20)

主引用文献

Kumar, J.,Micka, M.,Komarek, J.,Klumpler, T.,Bystry, V.,Sprangers, R.,Barinka, C.,Bryja, V.,Tripsianes, K.
A class III ligand oscillates between internal and terminal binding modes as it engages with the Dishevelled PDZ domain.
Structure, 33:1362-, 2025

PubMed Abstract: One of the largest domain-motif interactomes in human involves PSD-95/Discs-large/ZO-1 (PDZ) domains. The framework for understanding the PDZ interactome is well established; however the functional dynamics associated with PDZ-ligand interactions are poorly understood. Here, we report a dual PDZ-binding mode that ascribes unique dynamic features to class III ligand recognition. The crystal structure revealed that the PDZ domain can recognize either of the carboxylate moieties (terminal or internal) present in the class III ligand and laid out the register rules responsible for the dual recognition. Variants of the ligand designed to retain one or the other carboxylate of the native sequence were sufficient for PDZ binding. The conformational dynamics of PDZ probed by NMR relaxation dispersion experiments demonstrated that the class III ligand is shuffling binding modes as it engages with the PDZ domain. Our mechanistic findings reveal yet another aspect of PDZ binding plasticity specific to class III ligands.

PubMed: 40516532
DOI: 10.1016/j.str.2025.05.012

実験手法

X-RAY DIFFRACTION (1.36 Å)