Ingmundson Alyssa, Delprato Anna, Lambright David G, Roy Craig R
Section of Microbial Pathogenesis, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, Connecticut 06536, USA.
Nature. 2007 Nov 15;450(7168):365-9. doi: 10.1038/nature06336. Epub 2007 Oct 21.
Rab1 is a GTPase that regulates the transport of endoplasmic-reticulum-derived vesicles in eukaryotic cells. The intracellular pathogen Legionella pneumophila subverts Rab1 function to create a vacuole that supports bacterial replication by a mechanism that is not well understood. Here we describe L. pneumophila proteins that control Rab1 activity directly. We show that a region in the DrrA (defect in Rab1 recruitment A) protein required for recruitment of Rab1 to membranes functions as a guanine nucleotide dissociation inhibitor displacement factor. A second region of the DrrA protein stimulated Rab1 activation by functioning as a guanine nucleotide exchange factor. The LepB protein was found to inactivate Rab1 by stimulating GTP hydrolysis, indicating that LepB has GTPase-activating protein activity that regulates removal of Rab proteins from membranes. Thus, L. pneumophila encodes proteins that regulate three distinct biochemical reactions critical for Rab GTPase membrane cycling to redirect Rab1 to the pathogen-occupied vacuole and to control Rab1 function.
Rab1是一种鸟苷三磷酸酶（GTPase），可调节真核细胞中源自内质网的囊泡运输。细胞内病原体嗜肺军团菌破坏Rab1功能，通过一种尚未完全了解的机制形成一个支持细菌复制的液泡。在这里，我们描述了直接控制Rab1活性的嗜肺军团菌蛋白质。我们表明，DrrA（Rab1募集缺陷A）蛋白中负责将Rab1募集到膜上的区域，起着鸟嘌呤核苷酸解离抑制剂置换因子的作用。DrrA蛋白的第二个区域通过充当鸟嘌呤核苷酸交换因子来刺激Rab1激活。发现LepB蛋白通过刺激GTP水解使Rab1失活，这表明LepB具有鸟苷三磷酸酶激活蛋白活性，可调节Rab蛋白从膜上的去除。因此，嗜肺军团菌编码调节对Rab GTPase膜循环至关重要的三种不同生化反应的蛋白质，以将Rab1重定向到病原体占据的液泡并控制Rab1功能。
