Lpg0393 of Legionella pneumophila Is a Guanine-Nucleotide Exchange Factor for Rab5, Rab21 and Rab22

Varp is a Rab21 guanine nucleotide exchange factor and regulates endosome dynamics.

The small GTPases Rab5 and Rab21 are closely related, and play essential roles in endocytic trafficking. Rab5 is regulated by VPS9-domain-containing guanine nucleotide exchange factors. Here, we describe a new VPS9-domain protein with ankyrin repeats, the VPS9-ankyrin-repeat protein (Varp). Varp interacts preferentially with GDP-bound Rab21 and has a much stronger guanine nucleotide exchange ac...

VipD of Legionella pneumophila Targets Activated Rab5 and Rab22 to Interfere with Endosomal Trafficking in Macrophages

Upon phagocytosis, Legionella pneumophila translocates numerous effector proteins into host cells to perturb cellular metabolism and immunity, ultimately establishing intracellular survival and growth. VipD of L. pneumophila belongs to a family of bacterial effectors that contain the N-terminal lipase domain and the C-terminal domain with an unknown function. We report the crystal structure of ...

The structure of RalF, an Arf guanine nucleotide exchange factor from Legionella pneumophila, reveals the presence of a cap over the active site

The taming of a Rab GTPase by Legionella pneumophila

Small GTPases of the Rab family represent an attractive target for microbial pathogens due to their role in controlling many aspects of intracellular cargo transport. Legionella pneumophila is an intravacuolar pathogen that survives inside host cells by manipulating protein trafficking pathways through a number of effector proteins secreted by the bacterium. These act as functional mimics of ho...

Rabex-5 determines the neurite localization of its downstream Rab proteins in hippocampal neurons

Rab family small GTPases function as molecular switches in the regulation of membrane traffic, and their activity is thought to be controlled by guanine nucleotide exchange factors (GEFs). However, the role of GEFs in targeting Rab proteins to specific membrane compartments is poorly understood. We have recently reported finding that Rabex-5, originally described as a Rab5-GEF, also functions a...