1. Lpg0393 of Legionella pneumophila is a guanine-nucleotide exchange factor for Rab5, Rab21 and Rab22.
- Author
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Sohn YS, Shin HC, Park WS, Ge J, Kim CH, Lee BL, Heo WD, Jung JU, Rigden DJ, and Oh BH
- Subjects
- Amino Acid Sequence, Bacterial Proteins chemistry, Golgi Apparatus metabolism, Guanine Nucleotide Exchange Factors chemistry, Humans, Models, Molecular, Molecular Sequence Data, Protein Binding, Protein Conformation, Protein Interaction Domains and Motifs, Protein Transport, Sequence Alignment, rab GTP-Binding Proteins chemistry, rab5 GTP-Binding Proteins, Bacterial Proteins metabolism, Guanine Nucleotide Exchange Factors metabolism, Legionella pneumophila metabolism, rab GTP-Binding Proteins metabolism
- Abstract
Legionella pneumophila, a human intracellular pathogen, encodes about 290 effector proteins that are translocated into host cells through a secretion machinery. Some of these proteins have been shown to manipulate or subvert cellular processes during infection, but functional roles of a majority of them remain unknown. Lpg0393 is a newly identified Legionella effector classified as a hypothetical protein. Through X-ray crystallographic analysis, we show that Lpg0393 contains a Vps9-like domain, which is structurally most similar to the catalytic core of human Rabex-5 that activates the endosomal Rab proteins Rab5, Rab21 and Rab22. Consistently, Lpg0393 exhibited a guanine-nucleotide exchange factor activity toward the endosomal Rabs. This work identifies the first example of a bacterial guanine-nucleotide exchange factor that is active towards the Rab5 sub-cluster members, implying that the activation of these Rab proteins might be advantageous for the intracellular survival of Legionella.
- Published
- 2015
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