Crystal structure of the NEMO ubiquitin‐binding domain in complex with Lys 63‐linked di‐ubiquitin
Crystal structure of the NEMO ubiquitin‐binding domain in complex with Lys 63‐linked di‐ubiquitin
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DOI：
10.1016/j.febslet.2009.09.028
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发表时间：
2009-10
期刊：
影响因子：
3.5
通讯作者：
A. Yoshikawa;Yusuke Sato;M. Yamashita;Hisatoshi Mimura;A. Yamagata;S. Fukai
中科院分区：
文献类型：
--
作者：
A. Yoshikawa;Yusuke Sato;M. Yamashita;Hisatoshi Mimura;A. Yamagata;S. Fukai
NEMO是激活由蛋白质泛素化调节的NF-κB信号通路所必需的。据报道，NEMO的C末端亮氨酸拉链及其邻近的卷曲区域(CC2-LZ)以1μM亲和力与线性泛素链结合，以100μM亲和力与赖氨酸63链结合。本文报道了小鼠NEMO的CC2-LZ区与Lys_(63)连接的二泛素(K63-UB_2)络合物的晶体结构。泛素结合区由一个130？长的螺旋组成，形成一个平行的盘状二聚体。以Ile44为中心的泛素疏水斑块在Nemo泛素结合区的中部被识别。NEMO通过一个单一的泛素结合位点与每个K63-Ub2相互作用，这与与K63-Ub2的低亲和力结合一致。结构摘要：MINT-7262681：NEMO(uniprotkb：O88522)通过下拉(MI：0096)与泛素(uniprotkb：P62991)结合(MI：0407)：泛素(uniprotkb：P62991)和NEMO(uniprotkb：O88522)结合(MI：0407)
NEMO is essential for activation of the NF-κB signaling pathway, which is regulated by ubiquitination of proteins. The C-terminal leucine zipper of NEMO and its adjacent coiled-coil region (CC2-LZ) reportedly bind to linear ubiquitin chains with 1μM affinity and to Lys 63-linked chains with 100μM affinity. Here we report the crystal structure of the CC2-LZ region of mouse NEMO in complex with Lys 63-linked di-ubiquitin (K63-Ub2) at 2.7Å resolution. The ubiquitin-binding region consists of a 130Å-long helix and forms a parallel coiled-coil dimer. The Ile 44-centered hydrophobic patch of ubiquitin is recognized in the middle of the NEMO ubiquitin-binding region. NEMO interacts with each K63-Ub2via a single ubiquitin-binding site, consistent with low affinity binding with K63-Ub2. STRUCTURED SUMMARY: MINT-7262681: NEMO (uniprotkb:O88522) binds (MI:0407) to Ubiquitin (uniprotkb:P62991) by pull down (MI:0096) MINT-7262667: Ubiquitin (uniprotkb:P62991) and NEMO (uniprotkb:O88522) bind (MI:0407) by X-ray crystallography (MI:0114)