Structural basis for substrate recognition by a unique Legionella phosphoinositide phosphatase
Structural basis for substrate recognition by a unique Legionella phosphoinositide phosphatase
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DOI：
10.1073/pnas.1207903109
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发表时间：
2012-08-21
影响因子：
11.1
通讯作者：
Mao, Yuxin
中科院分区：
文献类型：
--
作者：
Hsu, FoSheng;Zhu, Wenhan;Mao, Yuxin
嗜肺军团菌是一种机会性细胞内病原体，可引起军团病的散发和流行病例。新出现的数据表明军团菌感染涉及宿主磷酸肌苷（PI）代谢的颠覆。然而，这种细菌如何主动操纵PI脂质以有利于其感染仍然是一个谜。在这里，我们报道了嗜肺乳杆菌毒力因子SidF是一种磷脂酰肌醇多磷酸3-磷酸酶，可以特异性水解PI(3,4)P-2和PI(3,4,5)P-3的D3磷酸。这种活性是将PI(4) p结合效应物锚定在细菌吞噬体上所必需的。SidF及其配合物与底物PI(3,4)P-2的晶体结构揭示了催化位点残基的惊人构象重排，形成一个阳离子袋，专门容纳底物的D4磷酸基团。因此，我们的发现揭示了一种独特的军团菌PI磷酸酶对建立细菌吞噬体的脂质特性至关重要。
Legionella pneumophila is an opportunistic intracellular pathogen that causes sporadic and epidemic cases of Legionnaires' disease. Emerging data suggest that Legionella infection involves the subversion of host phosphoinositide (PI) metabolism. However, how this bacterium actively manipulates PI lipids to benefit its infection is still an enigma. Here, we report that the L. pneumophila virulence factor SidF is a phosphatidylinositol polyphosphate 3-phosphatase that specifically hydrolyzes the D3 phosphate of PI(3,4)P-2 and PI(3,4,5)P-3. This activity is necessary for anchoring of PI(4)P-binding effectors to bacterial phagosomes. Crystal structures of SidF and its complex with its substrate PI(3,4)P-2 reveal striking conformational rearrangement of residues at the catalytic site to form a cationic pocket that specifically accommodates the D4 phosphate group of the substrate. Thus, our findings unveil a unique Legionella PI phosphatase essential for the establishment of lipid identity of bacterial phagosomes.