Specific Recognition of Linear Ubiquitin Chains by NEMO Is Important for NF-κB Activation

Simin Rahighi, Fumiyo Ikeda, Masato Kawasaki, Masato Akutsu, Nobuhiro Suzuki, Ryuichi Kato, Tobias Kensche, Tamami Uejima, Stuart Bloor, David Komander, Felix Randow, Soichi Wakatsuki, Ivan Dikic

研究成果: Contribution to journalArticle査読

519 被引用数 (Scopus)

抄録

Activation of nuclear factor-κB (NF-κB), a key mediator of inducible transcription in immunity, requires binding of NF-κB 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-κB 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-κB activation by TNF-α and other agonists, providing an explanation for the detrimental effect of NEMO mutations in patients suffering from X-linked ectodermal dysplasia and immunodeficiency.

本文言語英語
ページ(範囲)1098-1109
ページ数12
ジャーナルCell
136
6
DOI
出版ステータス出版済み - 3 20 2009
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生化学、遺伝学、分子生物学(全般)

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