4OWF

Crystal structure of the NEMO CoZi in complex with HOIP NZF1 domain

4OWF の概要

• エントリーDOI: 10.2210/pdb4owf/pdb
• 分子名称: NF-kappa-B essential modulator, E3 ubiquitin-protein ligase RNF31, ZINC ION, ... (4 entities in total)
• 機能のキーワード: lubac, nf-kappa b, nemo, hoip, transcription-protein binding complex, transcription/protein binding
• 由来する生物種: Mus musculus; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 24678.54

構造登録者

Rahighi, S.,Fujita, H.,Kawasaki, M.,Kato, R.,Iwai, K.,Wakatsuki, S. (登録日: 2014-01-31, 公開日: 2014-02-12, 最終更新日: 2023-09-27)

主引用文献

Fujita, H.,Rahighi, S.,Akita, M.,Kato, R.,Sasaki, Y.,Wakatsuki, S.,Iwai, K.
Mechanism Underlying I kappa B Kinase Activation Mediated by the Linear Ubiquitin Chain Assembly Complex.
Mol.Cell.Biol., 34:1322-1335, 2014

PubMed Abstract: The linear ubiquitin chain assembly complex (LUBAC) ligase, consisting of HOIL-1L, HOIP, and SHARPIN, specifically generates linear polyubiquitin chains. LUBAC-mediated linear polyubiquitination has been implicated in NF-κB activation. NEMO, a component of the IκB kinase (IKK) complex, is a substrate of LUBAC, but the precise molecular mechanism underlying linear chain-mediated NF-κB activation has not been fully elucidated. Here, we demonstrate that linearly polyubiquitinated NEMO activates IKK more potently than unanchored linear chains. In mutational analyses based on the crystal structure of the complex between the HOIP NZF1 and NEMO CC2-LZ domains, which are involved in the HOIP-NEMO interaction, NEMO mutations that impaired linear ubiquitin recognition activity and prevented recognition by LUBAC synergistically suppressed signal-induced NF-κB activation. HOIP NZF1 bound to NEMO and ubiquitin simultaneously, and HOIP NZF1 mutants defective in interaction with either NEMO or ubiquitin could not restore signal-induced NF-κB activation. Furthermore, linear chain-mediated activation of IKK2 involved homotypic interaction of the IKK2 kinase domain. Collectively, these results demonstrate that linear polyubiquitination of NEMO plays crucial roles in IKK activation and that this modification involves the HOIP NZF1 domain and recognition of NEMO-conjugated linear ubiquitin chains by NEMO on another IKK complex.

PubMed: 24469399
DOI: 10.1128/MCB.01538-13

実験手法

X-RAY DIFFRACTION (2 Å)