The Zinc Finger of NEMO Is a Functional Ubiquitin-binding Domain
The Zinc Finger of NEMO Is a Functional Ubiquitin-binding Domain
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DOI：
10.1074/jbc.m806655200
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发表时间：
2009-01-30
影响因子：
4.8
通讯作者：
Agou, Fabrice
中科院分区：
文献类型：
--
作者：
Cordier, Florence;Grubisha, Olivera;Agou, Fabrice
NEMO （NF-kappa B必需调节剂）是NF-kappa B信号通路的一种必需调节蛋白，主要参与免疫和炎症反应、细胞凋亡和肿瘤发生。在这里，我们报道了锌指（ZF）基序列，位于NEMO的调节c端一半，与泛素形成特定的复合物。我们研究了NEMO zf -泛素相互作用，并基于核磁共振、荧光和诱变数据，以及与DNA修复中泛素结合聚合酶eta锌指的序列同源性，提出了一个复合物的结构模型。功能互补分析和体内下拉实验进一步表明，参与泛素结合的ZF残基在功能上很重要，并且是nf - κ B信号传导对肿瘤坏死因子α的反应所必需的。因此，我们的研究结果表明NEMO ZF是泛素结合锌指型的真正泛素结合结构域。
NEMO (NF-kappa B essential modulator) is a regulatory protein essential to the canonical NF-kappa B signaling pathway, notably involved in immune and inflammatory responses, apoptosis, and oncogenesis. Here, we report that the zinc finger (ZF) motif, located in the regulatory C-terminal half of NEMO, forms a specific complex with ubiquitin. We have investigated the NEMO ZF-ubiquitin interaction and proposed a structural model of the complex based on NMR, fluorescence, and mutagenesis data and on the sequence homology with the polymerase eta ubiquitin-binding zinc finger involved in DNA repair. Functional complementation assays and in vivo pull-down experiments further show that ZF residues involved in ubiquitin binding are functionally important and required for NF-kappa B signaling in response to tumor necrosis factor-alpha. Thus, our findings indicate that NEMO ZF is a bona fide ubiquitin-binding domain of the ubiquitin-binding zinc finger type.