Mechanism of Rab1b deactivation by the Legionella pneumophila GAP LepB

Emerich Mihai Gazdag; Alexandra Streller; Ina Haneburger; Hubert Hilbi; Ingrid R. Vetter; Roger S. Goody; Aymelt Itzen

doi:10.1038/embor.2012.211

Mechanism of Rab1b deactivation by the Legionella pneumophila GAP LepB

Emerich Mihai Gazdag, Alexandra Streller, Ina Haneburger, Hubert Hilbi, Ingrid R. Vetter, Roger S. Goody, Aymelt Itzen

Associate Professorship of Silicon Chemistry

Research output: Contribution to journal › Article › peer-review

53 Scopus citations

Abstract

Legionella pneumophila is an intracellularly surviving pathogen that releases about 270 different proteins into the host cell during infection. A set of secreted proteins takes control of the vesicular trafficking regulator Rab1. Legionella LepB inactivates Rab1 by acting as a GTPase-activating protein (GAP). We present the crystal structure of the Rab1b:LepB complex together with a thorough biochemical analysis and show that the GAP domain of LepB consists of an unusual fold. LepB acts by an atypical RabGAP mechanism that is reminiscent of classical GAPs and therefore sets the protein apart from mammalian TBC-like GAPs. Surprisingly, LepB can function as a GAP for Rab3, Rab8, Rab13 and Rab35, too, suggesting that it has a broader cellular role than previously thought.

Original language	English
Pages (from-to)	199-205
Number of pages	7
Journal	EMBO Reports
Volume	14
Issue number	2
DOIs	https://doi.org/10.1038/embor.2012.211
State	Published - Feb 2013

Keywords

Legionnaires' disease GTPase
pathogen vacuole
vesicular trafficking

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10.1038/embor.2012.211

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title = "Mechanism of Rab1b deactivation by the Legionella pneumophila GAP LepB",

abstract = "Legionella pneumophila is an intracellularly surviving pathogen that releases about 270 different proteins into the host cell during infection. A set of secreted proteins takes control of the vesicular trafficking regulator Rab1. Legionella LepB inactivates Rab1 by acting as a GTPase-activating protein (GAP). We present the crystal structure of the Rab1b:LepB complex together with a thorough biochemical analysis and show that the GAP domain of LepB consists of an unusual fold. LepB acts by an atypical RabGAP mechanism that is reminiscent of classical GAPs and therefore sets the protein apart from mammalian TBC-like GAPs. Surprisingly, LepB can function as a GAP for Rab3, Rab8, Rab13 and Rab35, too, suggesting that it has a broader cellular role than previously thought.",

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AU - Hilbi, Hubert

AU - Vetter, Ingrid R.

AU - Goody, Roger S.

AU - Itzen, Aymelt

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Mechanism of Rab1b deactivation by the Legionella pneumophila GAP LepB

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