Catch and release: Rab1 exploitation by Legionella pneumophila.
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ABSTRACT:
SUBMITTER: Machner MP
PROVIDER: S-EPMC3265925 | biostudies-other | 2011 Jul
REPOSITORIES: biostudies-other
Publications
Catch and release: Rab1 exploitation by Legionella pneumophila.
Machner Matthias P MP Chen Yang Y
Cellular logistics 20110701 4
The intracellular pathogen Legionella pneumophila exploits host cell vesicular transport by manipulating the activity of the small GTPase Rab1. Bacterial proteins, so called effectors, that are delivered into the infected cell play a key role in this process. Here, we summarize recent developments in our quest to understand the molecular function of these effectors, and describe how L. pneumophila employs post-translational modification in a reversible manner to manipulate the activity of Rab1 o ...[more]
Similar Datasets
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Project description:The intracellular pathogen Legionella pneumophila hijacks the endoplasmic reticulum (ER)-derived vesicles to create an organelle designated Legionella-containing vacuole (LCV) required for bacterial replication. Maturation of the LCV involved acquisition of Rab1, which is mediated by the bacterial effector protein SidM/DrrA. SidM/DrrA is a bifunctional enzyme having the activity of both Rab1-specific GDP dissociation inhibitor (GDI) displacement factor (GDF) and guanine nucleotide exchange factor (GEF). LidA, another Rab1-interacting bacterial effector protein, was reported to promote SidM/DrrA-mediated recruitment of Rab1 to the LCV as well. Here we report the crystal structures of LidA complexes with GDP- and GTP-bound Rab1 respectively. Structural comparison revealed that GDP-Rab1 bound by LidA exhibits an active and nearly identical conformation with that of GTP-Rab1, suggesting that LidA can disrupt the switch function of Rab1 and render it persistently active. As with GTP, LidA maintains GDP-Rab1 in the active conformation through interaction with its two conserved switch regions. Consistent with the structural observations, biochemical assays showed that LidA binds to GDP- and GTP-Rab1 equally well with an affinity approximately 7.5 nM. We propose that the tight interaction with Rab1 allows LidA to facilitate SidM/DrrA-catalyzed release of Rab1 from GDIs. Taken together, our results support a unique mechanism by which a bacterial effector protein regulates Rab1 recycling.
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