3F89

NEMO CoZi domain

3F89 の概要

• エントリーDOI: 10.2210/pdb3f89/pdb
• 関連するPDBエントリー: 2ZVN 2ZVO
• 分子名称: NF-kappa-B essential modulator (2 entities in total)
• 機能のキーワード: nf-kb signaling, ubiquitin binding, coiled coil, cytoplasm, metal-binding, nucleus, phosphoprotein, transcription, transcription regulation, ubl conjugation, zinc, zinc-finger
• 由来する生物種: Mus musculus (mouse)
• 細胞内の位置: Cytoplasm : O88522
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 21554.42

構造登録者

Rahighi, S.,Ikeda, F.,Kawasaki, M.,Akutsu, M.,Suzuki, N.,Kato, R.,Kensche, T.,Uejima, T.,Bloor, S.,Komander, D.,Randow, F.,Wakatsuki, S.,Dikic, I. (登録日: 2008-11-11, 公開日: 2009-03-24, 最終更新日: 2023-12-27)

主引用文献

Rahighi, S.,Ikeda, F.,Kawasaki, M.,Akutsu, M.,Suzuki, N.,Kato, R.,Kensche, T.,Uejima, T.,Bloor, S.,Komander, D.,Randow, F.,Wakatsuki, S.,Dikic, I.
Specific recognition of linear ubiquitin chains by NEMO is important for NF-kappaB activation
Cell(Cambridge,Mass.), 136:1098-1109, 2009

PubMed Abstract: Activation of nuclear factor-kappaB (NF-kappaB), a key mediator of inducible transcription in immunity, requires binding of NF-kappaB essential modulator (NEMO) to ubiquitinated substrates. Here, we report that the UBAN (ubiquitin binding in ABIN and NEMO) motif of NEMO selectively binds linear (head-to-tail) ubiquitin chains. Crystal structures of the UBAN motif revealed a parallel coiled-coil dimer that formed a heterotetrameric complex with two linear diubiquitin molecules. The UBAN dimer contacted all four ubiquitin moieties, and the integrity of each binding site was required for efficient NF-kappaB activation. Binding occurred via a surface on the proximal ubiquitin moiety and the canonical Ile44 surface on the distal one, thereby providing specificity for linear chain recognition. Residues of NEMO involved in binding linear ubiquitin chains are required for NF-kappaB activation by TNF-alpha and other agonists, providing an explanation for the detrimental effect of NEMO mutations in patients suffering from X-linked ectodermal dysplasia and immunodeficiency.

PubMed: 19303852
DOI: 10.1016/j.cell.2009.03.007

実験手法

X-RAY DIFFRACTION (2.8 Å)