4jw1

Crystal structure of N-terminal 618-residue fragment of LepB from Legionella pneumophila

spinqualitylabelsall models 4jw1, resolution 3.16Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4jw1 is a 2 chain structure with sequence from Legionella pneumophila. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: FLC, GOL, MSE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q6X1Y7_LEGPN 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.

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