3WP0

Crystal structure of Dlg GK in complex with a phosphor-Lgl2 peptide

3WP0 の概要

• エントリーDOI: 10.2210/pdb3wp0/pdb
• 関連するPDBエントリー: 3WP1
• 分子名称: Disks large homolog 4, Lethal(2) giant larvae protein homolog 2, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: maguk, phosphorylation, cell polarity, tumor suppressors, phosphorylation dependent, peptide binding protein
• 由来する生物種: Rattus norvegicus (brown rat,rat,rats); 詳細
• 細胞内の位置: Cell membrane; Peripheral membrane protein: P31016; Cytoplasm: Q6P1M3
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 23920.93

構造登録者

Zhu, J.,Shang, Y.,Wan, Q.,Xia, Y.,Chen, J.,Du, Q.,Zhang, M. (登録日: 2014-01-08, 公開日: 2014-03-19, 最終更新日: 2024-11-13)

主引用文献

Zhu, J.,Shang, Y.,Wan, Q.,Xia, Y.,Chen, J.,Du, Q.,Zhang, M.
Phosphorylation-dependent interaction between tumor suppressors Dlg and Lgl
Cell Res., 24:451-463, 2014

PubMed Abstract: The tumor suppressors Discs Large (Dlg), Lethal giant larvae (Lgl) and Scribble are essential for the establishment and maintenance of epithelial cell polarity in metazoan. Dlg, Lgl and Scribble are known to interact strongly with each other genetically and form the evolutionarily conserved Scribble complex. Despite more than a decade of extensive research, it has not been demonstrated whether Dlg, Lgl and Scribble physically interact with each other. Here, we show that Dlg directly interacts with Lgl in a phosphorylation-dependent manner. Phosphorylation of any one of the three conserved Ser residues situated in the central linker region of Lgl is sufficient for its binding to the Dlg guanylate kinase (GK) domain. The crystal structures of the Dlg4 GK domain in complex with two phosphor-Lgl2 peptides reveal the molecular mechanism underlying the specific and phosphorylation-dependent Dlg/Lgl complex formation. In addition to providing a mechanistic basis underlying the regulated formation of the Scribble complex, the structure of the Dlg/Lgl complex may also serve as a starting point for designing specific Dlg inhibitors for targeting the Scribble complex formation.

PubMed: 24513855
DOI: 10.1038/cr.2014.16

実験手法

X-RAY DIFFRACTION (2.039 Å)