期刊
NATURE MICROBIOLOGY
卷 2, 期 3, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nmicrobiol.2016.236
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资金
- National Key Research and Development Project on Protein Machinery and its Control and Regulation of Biological Processes [2016YFA0501500]
- China National Science Foundation [31225002, 31461143006]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDB08020202]
- National Basic Research Program of China 973 Program [2014CB849602]
- Howard Hughes Medical Institute
- Beijing Scholar Program
Legionella pneumophila, the causative bacterium for Legionnaires' disease, hijacks host membrane trafficking for the maturation of the Legionella-containing vacuole (LCV). The LCV membrane mainly contains PtdIns4P, which is important for anchoring many secreted Legionella effectors onto the LCV. Here, we identify a cryptic functional domain (LepB_NTD) preceding the well-characterized RabGAP domain in the Legionella Dot/Icm type IV secretion system effector LepB. LepB_NTD alone is toxic to yeast and can disrupt the Golgi in mammalian cells. The crystal structure reveals an unexpected kinase fold and catalytic motif important for LepB_NTD function in eukaryotes. Cell biology-guided biochemical analyses uncovered a lipid kinase activity in LepB_NTD that specifically converts PtdIns3P into PtdIns(3,4) P-2. PtdIns(3,4) P 2 is efficiently hydrolysed into PtdIns4P by another Dot/Icm effector SidF that is known to possess phosphoinositide phosphatase activity. Consistently, SidF is capable of counteracting the cellular functions of LepB_NTD. Genetic analyses show a requirement for LepB kinase activity as well as lipid phosphatase activity of SidF for PtdIns4P biosynthesis on the LCV membrane. Our study identifies an unprecedented phosphatidylinositide 4-kinase activity from bacteria and highlights a sophisticated manipulation of host phosphoinositide metabolism by a bacterial pathogen.
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