2LC7

Solution structure of the isolated Par-6 PDZ domain

2LC7 の概要

• エントリーDOI: 10.2210/pdb2lc7/pdb
• 関連するPDBエントリー: 2LC6
• NMR情報: BMRB: 17600
• 分子名称: Par-6 (1 entity in total)
• 機能のキーワード: crib, allostery, cell polarity, cell adhesion
• 由来する生物種: Drosophila melanogaster (Fruit fly)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 10926.46

構造登録者

Volkman, B.F.,Whitney, D.S.,Peterson, F.C. (登録日: 2011-04-25, 公開日: 2011-11-30, 最終更新日: 2024-05-15)

主引用文献

Whitney, D.S.,Peterson, F.C.,Volkman, B.F.
A Conformational Switch in the CRIB-PDZ Module of Par-6.
Structure, 19:1711-1722, 2011

PubMed Abstract: Here, we report a novel mechanism of PDZ (PSD-95/Dlg/ZO-1) domain regulation that distorts a conserved element of PDZ ligand recognition. The polarity regulator Par-6 assembles a conserved multiprotein complex and is directly modulated by the Rho GTPase Cdc42. Cdc42 binds the adjacent Cdc42/Rac interactive binding (CRIB) and PDZ domains of Par-6, increasing C-terminal ligand binding affinity by 10-fold. By solving structures of the isolated PDZ domain and a disulfide-stabilized CRIB-PDZ, we detected a conformational switch that controls affinity by altering the configuration of the conserved "GLGF" loop. As a result, lysine 165 is displaced from the PDZ core by an adjacent hydrophobic residue, disrupting coordination of the PDZ ligand-binding cleft. Stabilization of the CRIB:PDZ interface restores K165 to its canonical location in the binding pocket. We conclude that a unique "dipeptide switch" in the Par-6 PDZ transmits a signal for allosteric activation to the ligand-binding pocket.

PubMed: 22078569
DOI: 10.1016/j.str.2011.07.018

実験手法

SOLUTION NMR