The taming of a Rab GTPase by Legionella pneumophila.
Small GTPases of the Rab family represent an attractive target for microbial pathogens due to their role in controlling many aspects of intracellular cargo transport. Legionella pneumophila is an intravacuolar pathogen that survives inside host cells by manipulating protein trafficking pathways through a number of effector proteins secreted by the bacterium. These act as functional mimics of host proteins that modulate the activity of switch proteins such as guanosine triphosphatases (GTPases). L. pneumophila exploits the ER (endoplasmic reticulum)-to-Golgi vesicle transport pathway by modifying activity of Rab1, the GTPase regulating this pathway. This pathogen recruits Rab1 to the vacuole in which it resides, where effector proteins located on the surface of the vacuole regulate the activity status of Rab1 by mimicking the function of a guanine dissociation inhibitor (GDI) displacement factor, guanine exchange factor (GEF), or a GTPase-activating protein (GAP). In addition to these non-covalent modifications that alter the nucleotide binding state of Rab1, the bacterium also uses covalent modifications such as adenylylation (AMPylation) to control the dynamic of Rab1 on the Legionella-containing vacuole. Remarkably, AMPylation of Rab1 by SidM can be reversed by the L. pneumophila effector protein SidD, which exhibits de-AMPylation activity, demonstrating that L. pneumophila and related pathogens may utilize covalent modifications in order to transiently alter the activity of host proteins.
Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD USA.
M Ramona
MR
Neunuebel
Matthias P
MP
Machner
D000249:Adenosine Monophosphate / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D006801:Humans; D016952:Legionella pneumophila / Q000378:metabolism*; D014617:Vacuoles / Q000382:microbiology*; D020761:rab1 GTP-Binding Proteins / Q000378:metabolism*
D001426:Bacterial Proteins; D000249:Adenosine Monophosphate; D020761:rab1 GTP-Binding Proteins