Abstract：
The gram-negative bacterium, Legionella pneumophila is known to manipulate the host cellular functions. L. pneumophila secretes bacterial proteins called Legionella effectors into the host cytosol that are necessary for these manipulations. The Legionella effector Lpg1137 was identified as a serine protease responsible for the degradation of syntaxin 17 (Stx17). However, how Lpg1137 specifically recognizes and degrades Stx17 remained unknown. Given that Stx17 is localized in the ER, mitochondria-associated membrane (MAM), and mitochondria, Lpg1137 likely distributes to these compartments to recognize Stx17. Here, we show that the C-terminal region of Lpg1137 binds to phosphatidic acid (PA), a MAM and mitochondria-enriched phospholipid, and that this binding is required for the correct intracellular distribution of Lpg1137. Two basic residues in the C-terminal region of Lpg1137 are required for PA binding and their mutation causes mislocalization of Lpg1137. This mutant also fails to degrade Stx17 while retaining protease activity. Taken together, our data reveal that Lpg1137 utilizes PA for its distribution to the membranous compartments in which Stx17 is localized.
摘要：
革兰氏阴性细菌,已知嗜肺军团菌操纵宿主细胞功能。嗜肺乳杆菌将称为军团菌效应物的细菌蛋白质分泌到宿主胞质溶胶中，这是这些操作所必需的。军团菌效应物Lpg1137被鉴定为负责降解突触素17(Stx17)的丝氨酸蛋白酶。然而,Lpg1137如何特异性识别和降解Stx17仍然未知。鉴于Stx17位于ER中，线粒体相关膜（MAM），和线粒体，Lpg1137可能分布到这些区室以识别Stx17。这里,我们显示LPG1137的C端区域与磷脂酸（PA）结合，MAM和富含线粒体的磷脂，并且这种结合对于Lpg1137的正确细胞内分布是必需的。Lpg1137的C-末端区域中的两个碱性残基是PA结合所必需的,并且它们的突变导致Lpg1137的错误定位。该突变体也不能降解Stx17,同时保留蛋白酶活性。一起来看,我们的数据显示，Lpg1137利用PA将其分布到Stx17所在的膜区室。
