5WOU

Crystal Structure of drosophila melanogaster Scribble PDZ1 domain in complex with Guk-Holder

5WOU の概要

• エントリーDOI: 10.2210/pdb5wou/pdb
• 分子名称: Protein lap4, GUK-holder, isoform A, 1,2-ETHANEDIOL, ... (5 entities in total)
• 機能のキーワード: scribble, pdz domain, guk-holder, cell polarity, cell adhesion
• 由来する生物種: Drosophila melanogaster (Fruit fly); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 11870.57

構造登録者

Caria, S.,Kvansakul, M. (登録日: 2017-08-03, 公開日: 2018-02-28, 最終更新日: 2024-11-13)

主引用文献

Caria, S.,Magtoto, C.M.,Samiei, T.,Portela, M.,Lim, K.Y.B.,How, J.Y.,Stewart, B.Z.,Humbert, P.O.,Richardson, H.E.,Kvansakul, M.
Drosophila melanogasterGuk-holder interacts with the Scribbled PDZ1 domain and regulates epithelial development with Scribbled and Discs Large.
J. Biol. Chem., 293:4519-4531, 2018

PubMed Abstract: Epithelial cell polarity is controlled by components of the Scribble polarity module, and its regulation is critical for tissue architecture and cell proliferation and migration. In , the adaptor protein Guk-holder (Gukh) binds to the Scribbled (Scrib) and Discs Large (Dlg) components of the Scribble polarity module and plays an important role in the formation of neuromuscular junctions. However, Gukh's role in epithelial tissue formation and the molecular basis for the Scrib-Gukh interaction remain to be defined. We now show using isothermal titration calorimetry that the Scrib PDZ1 domain is the major site for an interaction with Gukh. Furthermore, we defined the structural basis of this interaction by determining the crystal structure of the Scrib PDZ1-Gukh complex. The C-terminal PDZ-binding motif of Gukh is located in the canonical ligand-binding groove of Scrib PDZ1 and utilizes an unusually extensive network of hydrogen bonds and ionic interactions to enable binding to PDZ1 with high affinity. We next examined the role of Gukh along with those of Scrib and Dlg in epithelial tissues and found that Gukh is expressed in larval-wing and eye-epithelial tissues and co-localizes with Scrib and Dlg at the apical cell cortex. Importantly, we show that Gukh functions with Scrib and Dlg in the development of epithelial tissues, with depletion of Gukh enhancing the eye- and wing-tissue defects caused by Scrib or Dlg depletion. Overall, our findings reveal that Scrib's PDZ1 domain functions in the interaction with Gukh and that the Scrib-Gukh interaction has a key role in epithelial tissue development in .

PubMed: 29378849
DOI: 10.1074/jbc.M117.817528

実験手法

X-RAY DIFFRACTION (1.55 Å)