Mechanism of Rab1b deactivation by the Legionella pneumophila GAP LepB
Mechanism of Rab1b deactivation by the Legionella pneumophila GAP LepB
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DOI：
10.1038/embor.2012.211
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发表时间：
2013-02-01
期刊：
影响因子：
7.7
通讯作者：
Itzen, Aymelt
中科院分区：
文献类型：
--
作者：
Gazdag, Emerich Mihai;Streller, Alexandra;Itzen, Aymelt
嗜肺军团菌是一种细胞内存活的病原体，在感染过程中向宿主细胞释放约270种不同的蛋白质。一组分泌的蛋白质控制着囊泡运输调节因子Rab1。军团菌LepB通过作为GTP酶激活蛋白(GAP)来灭活Rab1。我们给出了Rab1b：LepB络合物的晶体结构，并进行了彻底的生化分析，表明LepB的GAP结构域由一个不寻常的折叠组成。LepB通过一种非典型的RabGAP机制发挥作用，这让人想起经典的GAP，因此使蛋白质有别于哺乳动物TBC样的GAP。令人惊讶的是，LepB也可以作为Rab3、Rab8、Rab13和Rab35的间隙，这表明它具有比之前认为的更广泛的细胞作用。
Legionella pneumophila is an intracellularly surviving pathogen that releases about 270 different proteins into the host cell during infection. A set of secreted proteins takes control of the vesicular trafficking regulator Rab1. Legionella LepB inactivates Rab1 by acting as a GTPase-activating protein (GAP). We present the crystal structure of the Rab1b:LepB complex together with a thorough biochemical analysis and show that the GAP domain of LepB consists of an unusual fold. LepB acts by an atypical RabGAP mechanism that is reminiscent of classical GAPs and therefore sets the protein apart from mammalian TBC-like GAPs. Surprisingly, LepB can function as a GAP for Rab3, Rab8, Rab13 and Rab35, too, suggesting that it has a broader cellular role than previously thought.