2FLU

Crystal Structure of the Kelch-Neh2 Complex

2FLU の概要

• エントリーDOI: 10.2210/pdb2flu/pdb
• 関連するPDBエントリー: 1U6D 1ZGK
• 分子名称: Kelch-like ECH-associated protein 1, Nrf2 (3 entities in total)
• 機能のキーワード: kelch domain, protein-peptide complex, beta-propeller, ligase
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm, cytosol: Q16236
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 35552.54

構造登録者

Li, X.,Lo, J.,Beamer, L.,Hannink, M. (登録日: 2006-01-06, 公開日: 2006-08-15, 最終更新日: 2024-10-30)

主引用文献

Lo, S.C.,Li, X.,Henzl, M.T.,Beamer, L.J.,Hannink, M.
Structure of the Keap1:Nrf2 interface provides mechanistic insight into Nrf2 signaling.
Embo J., 25:3605-3617, 2006

PubMed Abstract: Keap1 is a BTB-Kelch substrate adaptor protein that regulates steady-state levels of Nrf2, a bZIP transcription factor, in response to oxidative stress. We have determined the structure of the Kelch domain of Keap1 bound to a 16-mer peptide from Nrf2 containing a highly conserved DxETGE motif. The Nrf2 peptide contains two short antiparallel beta-strands connected by two overlapping type I beta-turns stabilized by the aspartate and threonine residues. The beta-turn region fits into a binding pocket on the top face of the Kelch domain and the glutamate residues form multiple hydrogen bonds with highly conserved residues in Keap1. Mutagenesis experiments confirmed the role of individual amino acids for binding of Nrf2 to Keap1 and for Keap1-mediated repression of Nrf2-dependent gene expression. Our results provide a detailed picture of how a BTB-Kelch substrate adaptor protein binds to its cognate substrate and will enable the rational design of novel chemopreventive agents.

PubMed: 16888629
DOI: 10.1038/sj.emboj.7601243

実験手法

X-RAY DIFFRACTION (1.5 Å)