4jvs

Crystal structure of LepB GAP domain from Legionella drancourtii in complex with Rab1-GDP and AlF3Crystal structure of LepB GAP domain from Legionella drancourtii in complex with Rab1-GDP and AlF3

Structural highlights 4jvs is a 2 chain structure with sequence from Homo sapiens and Legionella drancourtii llap12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , , , Related: 4jw1 Gene: LDG_7216 (Legionella drancourtii LLAP12), RAB1A (Homo sapiens) Resources: FirstGlance, OCA, RCSB, PDBsum Function [RAB1A_HUMAN] Probably required for transit of protein from the ER through Golgi compartment. Binds GTP and GDP and possesses intrinsic GTPase activity. Publication Abstract from PubMed Rab GTPases are emerging targets of diverse bacterial pathogens. Here, we perform biochemical and structural analyses of LepB, a Rab GTPase-activating protein (GAP) effector from Legionella pneumophila. We map LepB GAP domain to residues 313-618 and show that the GAP domain is Rab1 specific with a catalytic activity higher than the canonical eukaryotic TBC GAP and the newly identified VirA/EspG family of bacterial RabGAP effectors. Exhaustive mutation analyses identify Arg444 as the arginine finger, but no catalytically essential glutamine residues. Crystal structures of LepB313-618 alone and the GAP domain of Legionella drancourtii LepB in complex with Rab1-GDP-AlF3 support the catalytic role of Arg444, and also further reveal a 3D architecture and a GTPase-binding mode distinct from all known GAPs. Glu449, structurally equivalent to TBC RabGAP glutamine finger in apo-LepB, undergoes a drastic movement upon Rab1 binding, which induces Rab1 Gln70 side-chain flipping towards GDP-AlF3 through a strong ionic interaction. This conformationally rearranged Gln70 acts as the catalytic cis-glutamine, therefore uncovering an unexpected RasGAP-like catalytic mechanism for LepB. Our studies highlight an extraordinary structural and catalytic diversity of RabGAPs, particularly those from bacterial pathogens.Cell Research advance online publication 16 April 2013; doi:10.1038/cr.2013.54. Structural analyses of Legionella LepB reveal a new GAP fold that catalytically mimics eukaryotic RasGAP.,Yu Q, Hu L, Yao Q, Zhu Y, Dong N, Wang DC, Shao F Cell Res. 2013 Apr 16. doi: 10.1038/cr.2013.54. PMID:23588383 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 4jvs, resolution 2.78Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image