Structural basis for specific recognition of Lys 63-linked polyubiquitin chains by NZF domains of TAB2 and TAB3
Structural basis for specific recognition of Lys 63-linked polyubiquitin chains by NZF domains of TAB2 and TAB3
复制标题
DOI：
10.1038/emboj.2009.345
复制
发表时间：
2009-12-16
期刊：
影响因子：
11.4
通讯作者：
Fukai, Shuya
中科院分区：
文献类型：
--
作者：
Sato, Yusuke;Yoshikawa, Azusa;Fukai, Shuya
Tab2和Tab3通过其NPL4锌指(NZF)结构域对Lys 63连接的多泛素链的特异性识别，激活Jun氨基末端激酶和核因子-kappa B通路。在这里，我们报道了Tab2和Tab3 NZF结构域在1.18埃和1.40埃分辨率下分别与Lys 63连接的二泛素形成的配合物的晶体结构。这两个NZF结构域都通过保守的Thr-Phe二肽与远端泛素结合，这对NPL4的NZF结构域与单泛素的相互作用是重要的。相反，Tab2和Tab3特异的表面结合了近端的泛素。Tab2和Tab3 NZF结构域的远端和近端结合部位都识别泛素上以Ile 44为中心的疏水斑块，但不与Lys 63连接的异肽键相互作用。诱变实验表明，这两个结合位点都是与赖氨酸63连接的二泛素结合所必需的。因此，我们提出了一种TAB2和Tab3 NZF结构域识别Lys 63连接的多泛素链的机制，其中二泛素单元被单个NZF结构域特异性识别。EMBO期刊(2009)28,3903-3909。DOI：10.1038/Intemj.2009.345；2009年11月19日在线发布
TAB2 and TAB3 activate the Jun N-terminal kinase and nuclear factor-kappa B pathways through the specific recognition of Lys 63-linked polyubiquitin chains by its Npl4 zinc-finger (NZF) domain. Here we report crystal structures of the TAB2 and TAB3 NZF domains in complex with Lys 63-linked diubiquitin at 1.18 and 1.40 angstrom resolutions, respectively. Both NZF domains bind to the distal ubiquitin through a conserved Thr-Phe dipeptide that has been shown to be important for the interaction of the NZF domain of Npl4 with monoubiquitin. In contrast, a surface specific to TAB2 and TAB3 binds the proximal ubiquitin. Both the distal and proximal binding sites of the TAB2 and TAB3 NZF domains recognize the Ile 44-centred hydrophobic patch on ubiquitin but do not interact with the Lys 63-linked isopeptide bond. Mutagenesis experiments show that both binding sites are required to enable binding of Lys 63-linked diubiquitin. We therefore propose a mechanism for the recognition of Lys 63-linked polyubiquitin chains by TAB2 and TAB3 NZF domains in which diubiquitin units are specifically recognized by a single NZF domain. The EMBO Journal (2009) 28, 3903-3909. doi: 10.1038/emboj.2009.345; Published online 19 November 2009