Structural basis for the recognition of Ubc13 by the Shigella flexneri effector OspI.
Structural basis for the recognition of Ubc13 by the Shigella flexneri effector OspI.
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DOI：
10.1016/j.jmb.2013.02.037
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发表时间：
2013-08
影响因子：
5.6
通讯作者：
A. Nishide;Minsoo Kim;K. Takagi;Ai Himeno;Takahito Sanada;C. Sasakawa;T. Mizushima
中科院分区：
文献类型：
--
作者：
A. Nishide;Minsoo Kim;K. Takagi;Ai Himeno;Takahito Sanada;C. Sasakawa;T. Mizushima
Ubc 13是一种泛素结合酶，在人类疾病的核因子-κB信号转导通路中起关键作用。福氏志贺菌OspI通过催化Ubc 13中100位谷氨酰胺残基的脱酰胺作用影响炎症反应。这种修饰阻止TNF（肿瘤坏死因子）受体相关因子6的活化，导致二酰基甘油-CBM（CARD-Bcl 10-Malt 1）复合物-TNF受体相关因子6-核因子-κB信号通路的调节。为了阐明OspI功能的结构基础，我们确定了催化惰性OspI C62 A突变体及其与Ubc 13的复合物的晶体结构，分辨率分别为3.0和2.96 μ m。OspI-Ubc 13复合物的结构表明，OspI和Ubc 13之间的相互作用表面是一个疏水表面和一个互补的带电表面。此外，我们预测OspI的互补带电表面在底物特异性测定中起着关键作用。
Ubc13 is a ubiquitin-conjugating enzyme that plays a key role in the nuclear factor-κB signal transduction pathway in human diseases. TheShigella flexnerieffector OspI affects inflammatory responses by catalyzing the deamidation of a specific glutamine residue at position 100 in Ubc13 during infection. This modification prevents the activation of the TNF (tumornecrosisfactor) receptor-associated factor 6, leading to modulation of the diacylglycerol–CBM (CARD–Bcl10–Malt1) complex–TNF receptor-associated factor 6–nuclear factor-κB signaling pathway. To elucidate the structural basis of OspI function, we determined the crystal structures of the catalytically inert OspI C62A mutant and its complex with Ubc13 at resolutions of 3.0 and 2.96 Å, respectively. The structure of the OspI–Ubc13 complex revealed that the interacting surfaces between OspI and Ubc13 are a hydrophobic surface and a complementary charged surface. Furthermore, we predict that the complementary charged surface of OspI plays a key role in substrate specificity determination.