5I7Z

Crystal structure of a Par-6 PDZ-Crumbs 3 C-terminal peptide complex

5I7Z の概要

• エントリーDOI: 10.2210/pdb5i7z/pdb
• 分子名称: LD29223p, Crb-3, DI(HYDROXYETHYL)ETHER, ... (4 entities in total)
• 機能のキーワード: pdz, cell polarity, signaling protein
• 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: 11340.05

構造登録者

Whitney, D.S.,Peterson, F.C.,Prehoda, K.E.,Volkman, B.F. (登録日: 2016-02-18, 公開日: 2016-03-16, 最終更新日: 2024-03-06)

主引用文献

Whitney, D.S.,Peterson, F.C.,Kittell, A.W.,Egner, J.M.,Prehoda, K.E.,Volkman, B.F.
Binding of Crumbs to the Par-6 CRIB-PDZ Module Is Regulated by Cdc42.
Biochemistry, 55:1455-1461, 2016

PubMed Abstract: Par-6 is a scaffold protein that organizes other proteins into a complex required to initiate and maintain cell polarity. Cdc42-GTP binds the CRIB module of Par-6 and alters the binding affinity of the adjoining PDZ domain. Allosteric regulation of the Par-6 PDZ domain was first demonstrated using a peptide identified in a screen of typical carboxyl-terminal ligands. Crumbs, a membrane protein that localizes a conserved polarity complex, was subsequently identified as a functional partner for Par-6 that likely interacts with the PDZ domain. Here we show by nuclear magnetic resonance that Par-6 binds a Crumbs carboxyl-terminal peptide and report the crystal structure of the PDZ-peptide complex. The Crumbs peptide binds Par-6 more tightly than the previously studied carboxyl peptide ligand and interacts with the CRIB-PDZ module in a Cdc42-dependent manner. The Crumbs:Par-6 crystal structure reveals specific PDZ-peptide contacts that contribute to its higher affinity and Cdc42-enhanced binding. Comparisons with existing structures suggest that multiple C-terminal Par-6 ligands respond to a common conformational switch that transmits the allosteric effects of GTPase binding.

PubMed: 26894406
DOI: 10.1021/acs.biochem.5b01342

実験手法

X-RAY DIFFRACTION (1.801 Å)