3TKL

Crystal structure of the GTP-bound Rab1a in complex with the coiled-coil domain of LidA from Legionella pneumophila

Summary for 3TKL

• Entry DOI: 10.2210/pdb3tkl/pdb
• Related: 3sfv
• Descriptor: Ras-related protein Rab-1A, LidA protein, substrate of the Dot/Icm system, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: vesicle trafficking, protein transport-protein binding complex, protein transport/protein binding
• Biological source: Homo sapiens (human); More
• Cellular location: Golgi apparatus: P62820
• Total number of polymer chains: 2
• Total formula weight: 52948.76

Authors

Cheng, W.,Yin, K.,Lu, D.,Li, B.,Zhu, D.,Chen, Y.,Zhang, H.,Xu, S.,Chai, J.,Gu, L. (deposition date: 2011-08-27, release date: 2012-06-27, Last modification date: 2023-11-01)

Primary citation

Cheng, W.,Yin, K.,Lu, D.,Li, B.,Zhu, D.,Chen, Y.,Zhang, H.,Xu, S.,Chai, J.,Gu, L.
Structural insights into a unique Legionella pneumophila effector LidA recognizing both GDP and GTP bound Rab1 in their active state
Plos Pathog., 8:e1002528-e1002528, 2012

PubMed Abstract: 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.

PubMed: 22416225
DOI: 10.1371/journal.ppat.1002528

Experimental method

X-RAY DIFFRACTION (2.183 Å)