4JVS

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

4JVS の概要

• エントリーDOI: 10.2210/pdb4jvs/pdb
• 関連するPDBエントリー: 4JW1
• 分子名称: Putative uncharacterized protein, Ras-related protein Rab-1A, ACETIC ACID, ... (7 entities in total)
• 機能のキーワード: new gap fold, bind and hydrolyze guanosine triphosphate, rab1 binding, hydrolase activator-protein transport complex, hydrolase activator/protein transport
• 由来する生物種: Legionella drancourtii; 詳細
• 細胞内の位置: Golgi apparatus: P62820
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 56723.11

構造登録者

Yu, Q.,Yao, Q.,Wang, D.-C.,Shao, F. (登録日: 2013-03-26, 公開日: 2013-05-08, 最終更新日: 2024-03-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.783 Å)