6XA6

Crystal Structure of Human Scribble PDZ3:Vangl2 Complex

6XA6 の概要

• エントリーDOI: 10.2210/pdb6xa6/pdb
• 分子名称: Protein scribble homolog, Vang-like protein 2, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: cell polarity, cytosolic protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 22067.13

構造登録者

How, J.Y.,Kvansakul, M. (登録日: 2020-06-04, 公開日: 2021-03-24, 最終更新日: 2023-10-18)

主引用文献

How, J.Y.,Stephens, R.K.,Lim, K.Y.B.,Humbert, P.O.,Kvansakul, M.
Structural basis of the human Scribble-Vangl2 association in health and disease.
Biochem.J., 478:1321-1332, 2021

PubMed Abstract: Scribble is a critical cell polarity regulator that has been shown to work as either an oncogene or tumor suppressor in a context dependent manner, and also impacts cell migration, tissue architecture and immunity. Mutations in Scribble lead to neural tube defects in mice and humans, which has been attributed to a loss of interaction with the planar cell polarity regulator Vangl2. We show that the Scribble PDZ domains 1, 2 and 3 are able to interact with the C-terminal PDZ binding motif of Vangl2 and have now determined crystal structures of these Scribble PDZ domains bound to the Vangl2 peptide. Mapping of mammalian neural tube defect mutations reveal that mutations located distal to the canonical PDZ domain ligand binding groove can not only ablate binding to Vangl2 but also disrupt binding to multiple other signaling regulators. Our findings suggest that PDZ-associated neural tube defect mutations in Scribble may not simply act in a Vangl2 dependent manner but as broad-spectrum loss of function mutants by disrupting the global Scribble-mediated interaction network.

PubMed: 33684218
DOI: 10.1042/BCJ20200816

実験手法

X-RAY DIFFRACTION (1.95 Å)