4JVS

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

Summary for 4JVS

• Entry DOI: 10.2210/pdb4jvs/pdb
• Related: 4JW1
• Descriptor: Putative uncharacterized protein, Ras-related protein Rab-1A, ACETIC ACID, ... (7 entities in total)
• Functional Keywords: new gap fold, bind and hydrolyze guanosine triphosphate, rab1 binding, hydrolase activator-protein transport complex, hydrolase activator/protein transport
• Biological source: Legionella drancourtii; More
• Cellular location: Golgi apparatus: P62820
• Total number of polymer chains: 2
• Total formula weight: 56723.11

Authors

Yu, Q.,Yao, Q.,Wang, D.-C.,Shao, F. (deposition date: 2013-03-26, release date: 2013-05-08, Last modification date: 2024-03-20)

Primary citation

Yu, Q.,Hu, L.,Yao, Q.,Zhu, Y.,Dong, N.,Wang, D.-C.,Shao, F.
Structural analyses of Legionella LepB reveal a new GAP fold that catalytically mimics eukaryotic RasGAP
Cell Res., 23:775-787, 2013

PubMed Abstract: 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.

PubMed: 23588383
DOI: 10.1038/cr.2013.54

Experimental method

X-RAY DIFFRACTION (2.783 Å)