Structural insights into a unique legionella pneumophila effector lida recognizing both gdp and gtp bound rab1 in their active state

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. © 2012 cheng et al.