title: Lpg0393 of Legionella pneumophila is a guanine-nucleotide exchange factor for Rab5, Rab21 and Rab22.
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.
authors.affiliation: Department of Biological Sciences, KAIST Institute for the Biocentury, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Korea.
authors.forename: Young-Sik
authors.initials: YS
authors.lastname: Sohn
authors.affiliation: Department of Biological Sciences, KAIST Institute for the Biocentury, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Korea; Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-600, Korea.
authors.forename: Ho-Chul
authors.initials: HC
authors.lastname: Shin
authors.affiliation: Department of Biological Sciences, KAIST Institute for the Biocentury, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Korea.
authors.forename: Wei Sun
authors.initials: WS
authors.lastname: Park
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Jianning
authors.initials: J
authors.lastname: Ge
authors.affiliation: Global Research Laboratory of Insect Symbiosis, College of Pharmacy, Pusan National University, Jangjeon Dong, Kumjeong Ku, Busan, 609-735, Korea.
authors.forename: Chan-Hee
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Global Research Laboratory of Insect Symbiosis, College of Pharmacy, Pusan National University, Jangjeon Dong, Kumjeong Ku, Busan, 609-735, Korea.
authors.forename: Bok Luel
authors.initials: BL
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, KAIST Institute for the Biocentury, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Korea.
authors.forename: Won Do
authors.initials: WD
authors.lastname: Heo
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Jae U
authors.initials: JU
authors.lastname: Jung
authors.affiliation: Institute of Integrative Biology, University of Liverpool, Crown St., Liverpool, L69 7ZB, United Kingdom.
authors.forename: Daniel John
authors.initials: DJ
authors.lastname: Rigden
authors.affiliation: Department of Biological Sciences, KAIST Institute for the Biocentury, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Korea.
authors.forename: Byung-Ha
authors.initials: BH
authors.lastname: Oh
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D016952:Legionella pneumophila / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D016415:Sequence Alignment; D020691:rab GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D020696:rab5 GTP-Binding Proteins
chemical_list: D001426:Bacterial Proteins; D020662:Guanine Nucleotide Exchange Factors; C415145:RAB21 protein, human; D020691:rab GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins
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