Lpg0393 of Legionella pneumophila Is a Guanine-Nucleotide Exchange Factor for Rab5, Rab21 and Rab22
Identifieur interne : 000026 ( Pmc/Curation ); précédent : 000025; suivant : 000027Lpg0393 of Legionella pneumophila Is a Guanine-Nucleotide Exchange Factor for Rab5, Rab21 and Rab22
Auteurs : Young-Sik Sohn [Corée du Sud] ; Ho-Chul Shin [Corée du Sud] ; Wei Sun Park [Corée du Sud] ; Jianning Ge [États-Unis] ; Chan-Hee Kim [Corée du Sud] ; Bok Luel Lee [Corée du Sud] ; Won Do Heo [Corée du Sud] ; Jae U. Jung [États-Unis] ; Daniel John Rigden [Royaume-Uni] ; Byung-Ha Oh [Corée du Sud]Source :
- PLoS ONE [ 1932-6203 ] ; 2015.
Abstract
Url:
DOI: 10.1371/journal.pone.0118683
PubMed: 25821953
PubMed Central: 4379102
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Lpg0393 of <italic>Legionella pneumophila</italic> Is a Guanine-Nucleotide Exchange Factor for Rab5, Rab21 and Rab22</title><author><name sortKey="Sohn, Young Sik" sort="Sohn, Young Sik" uniqKey="Sohn Y" first="Young-Sik" last="Sohn">Young-Sik Sohn</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Department of Biological Sciences, KAIST Institute for the Biocentury, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biological Sciences, KAIST Institute for the Biocentury, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology, Daejeon, 305-701</wicri:regionArea></affiliation></author><author><name sortKey="Shin, Ho Chul" sort="Shin, Ho Chul" uniqKey="Shin H" first="Ho-Chul" last="Shin">Ho-Chul Shin</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Department of Biological Sciences, KAIST Institute for the Biocentury, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biological Sciences, KAIST Institute for the Biocentury, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology, Daejeon, 305-701</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-600, Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-600</wicri:regionArea></affiliation></author><author><name sortKey="Park, Wei Sun" sort="Park, Wei Sun" uniqKey="Park W" first="Wei Sun" last="Park">Wei Sun Park</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Department of Biological Sciences, KAIST Institute for the Biocentury, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biological Sciences, KAIST Institute for the Biocentury, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology, Daejeon, 305-701</wicri:regionArea></affiliation></author><author><name sortKey="Ge, Jianning" sort="Ge, Jianning" uniqKey="Ge J" first="Jianning" last="Ge">Jianning Ge</name><affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California</wicri:regionArea></affiliation></author><author><name sortKey="Kim, Chan Hee" sort="Kim, Chan Hee" uniqKey="Kim C" first="Chan-Hee" last="Kim">Chan-Hee Kim</name><affiliation wicri:level="1"><nlm:aff id="aff004"><addr-line>Global Research Laboratory of Insect Symbiosis, College of Pharmacy, Pusan National University, Jangjeon Dong, Kumjeong Ku, Busan, 609-735, Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Global Research Laboratory of Insect Symbiosis, College of Pharmacy, Pusan National University, Jangjeon Dong, Kumjeong Ku, Busan, 609-735</wicri:regionArea></affiliation></author><author><name sortKey="Lee, Bok Luel" sort="Lee, Bok Luel" uniqKey="Lee B" first="Bok Luel" last="Lee">Bok Luel Lee</name><affiliation wicri:level="1"><nlm:aff id="aff004"><addr-line>Global Research Laboratory of Insect Symbiosis, College of Pharmacy, Pusan National University, Jangjeon Dong, Kumjeong Ku, Busan, 609-735, Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Global Research Laboratory of Insect Symbiosis, College of Pharmacy, Pusan National University, Jangjeon Dong, Kumjeong Ku, Busan, 609-735</wicri:regionArea></affiliation></author><author><name sortKey="Do Heo, Won" sort="Do Heo, Won" uniqKey="Do Heo W" first="Won" last="Do Heo">Won Do Heo</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Department of Biological Sciences, KAIST Institute for the Biocentury, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biological Sciences, KAIST Institute for the Biocentury, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology, Daejeon, 305-701</wicri:regionArea></affiliation></author><author><name sortKey="Jung, Jae U" sort="Jung, Jae U" uniqKey="Jung J" first="Jae U." last="Jung">Jae U. Jung</name><affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California</wicri:regionArea></affiliation></author><author><name sortKey="Rigden, Daniel John" sort="Rigden, Daniel John" uniqKey="Rigden D" first="Daniel John" last="Rigden">Daniel John Rigden</name><affiliation wicri:level="1"><nlm:aff id="aff005"><addr-line>Institute of Integrative Biology, University of Liverpool, Crown St., Liverpool, L69 7ZB, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Integrative Biology, University of Liverpool, Crown St., Liverpool, L69 7ZB</wicri:regionArea></affiliation></author><author><name sortKey="Oh, Byung Ha" sort="Oh, Byung Ha" uniqKey="Oh B" first="Byung-Ha" last="Oh">Byung-Ha Oh</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Department of Biological Sciences, KAIST Institute for the Biocentury, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biological Sciences, KAIST Institute for the Biocentury, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology, Daejeon, 305-701</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25821953</idno><idno type="pmc">4379102</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4379102</idno><idno type="RBID">PMC:4379102</idno><idno type="doi">10.1371/journal.pone.0118683</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000026</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000026</idno><idno type="wicri:Area/Pmc/Curation">000026</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000026</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Lpg0393 of <italic>Legionella pneumophila</italic> Is a Guanine-Nucleotide Exchange Factor for Rab5, Rab21 and Rab22</title><author><name sortKey="Sohn, Young Sik" sort="Sohn, Young Sik" uniqKey="Sohn Y" first="Young-Sik" last="Sohn">Young-Sik Sohn</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Department of Biological Sciences, KAIST Institute for the Biocentury, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biological Sciences, KAIST Institute for the Biocentury, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology, Daejeon, 305-701</wicri:regionArea></affiliation></author><author><name sortKey="Shin, Ho Chul" sort="Shin, Ho Chul" uniqKey="Shin H" first="Ho-Chul" last="Shin">Ho-Chul Shin</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Department of Biological Sciences, KAIST Institute for the Biocentury, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biological Sciences, KAIST Institute for the Biocentury, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology, Daejeon, 305-701</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-600, Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-600</wicri:regionArea></affiliation></author><author><name sortKey="Park, Wei Sun" sort="Park, Wei Sun" uniqKey="Park W" first="Wei Sun" last="Park">Wei Sun Park</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Department of Biological Sciences, KAIST Institute for the Biocentury, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biological Sciences, KAIST Institute for the Biocentury, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology, Daejeon, 305-701</wicri:regionArea></affiliation></author><author><name sortKey="Ge, Jianning" sort="Ge, Jianning" uniqKey="Ge J" first="Jianning" last="Ge">Jianning Ge</name><affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California</wicri:regionArea></affiliation></author><author><name sortKey="Kim, Chan Hee" sort="Kim, Chan Hee" uniqKey="Kim C" first="Chan-Hee" last="Kim">Chan-Hee Kim</name><affiliation wicri:level="1"><nlm:aff id="aff004"><addr-line>Global Research Laboratory of Insect Symbiosis, College of Pharmacy, Pusan National University, Jangjeon Dong, Kumjeong Ku, Busan, 609-735, Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Global Research Laboratory of Insect Symbiosis, College of Pharmacy, Pusan National University, Jangjeon Dong, Kumjeong Ku, Busan, 609-735</wicri:regionArea></affiliation></author><author><name sortKey="Lee, Bok Luel" sort="Lee, Bok Luel" uniqKey="Lee B" first="Bok Luel" last="Lee">Bok Luel Lee</name><affiliation wicri:level="1"><nlm:aff id="aff004"><addr-line>Global Research Laboratory of Insect Symbiosis, College of Pharmacy, Pusan National University, Jangjeon Dong, Kumjeong Ku, Busan, 609-735, Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Global Research Laboratory of Insect Symbiosis, College of Pharmacy, Pusan National University, Jangjeon Dong, Kumjeong Ku, Busan, 609-735</wicri:regionArea></affiliation></author><author><name sortKey="Do Heo, Won" sort="Do Heo, Won" uniqKey="Do Heo W" first="Won" last="Do Heo">Won Do Heo</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Department of Biological Sciences, KAIST Institute for the Biocentury, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biological Sciences, KAIST Institute for the Biocentury, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology, Daejeon, 305-701</wicri:regionArea></affiliation></author><author><name sortKey="Jung, Jae U" sort="Jung, Jae U" uniqKey="Jung J" first="Jae U." last="Jung">Jae U. Jung</name><affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California</wicri:regionArea></affiliation></author><author><name sortKey="Rigden, Daniel John" sort="Rigden, Daniel John" uniqKey="Rigden D" first="Daniel John" last="Rigden">Daniel John Rigden</name><affiliation wicri:level="1"><nlm:aff id="aff005"><addr-line>Institute of Integrative Biology, University of Liverpool, Crown St., Liverpool, L69 7ZB, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Integrative Biology, University of Liverpool, Crown St., Liverpool, L69 7ZB</wicri:regionArea></affiliation></author><author><name sortKey="Oh, Byung Ha" sort="Oh, Byung Ha" uniqKey="Oh B" first="Byung-Ha" last="Oh">Byung-Ha Oh</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Department of Biological Sciences, KAIST Institute for the Biocentury, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biological Sciences, KAIST Institute for the Biocentury, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology, Daejeon, 305-701</wicri:regionArea></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><italic>Legionella pneumophila</italic>, 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 <italic>Legionella</italic> 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 <italic>Legionella</italic>.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Kagan, Jc" uniqKey="Kagan J">JC Kagan</name></author><author><name sortKey="Stein, Mp" uniqKey="Stein M">MP Stein</name></author><author><name sortKey="Pypaert, M" uniqKey="Pypaert M">M Pypaert</name></author><author><name sortKey="Roy, Cr" uniqKey="Roy C">CR Roy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xu, L" uniqKey="Xu L">L Xu</name></author><author><name sortKey="Luo, Zq" uniqKey="Luo Z">ZQ Luo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tilney, Lg" uniqKey="Tilney L">LG Tilney</name></author><author><name sortKey="Harb, Os" 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<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS One</journal-id><journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plosone</journal-id><journal-title-group><journal-title>PLoS ONE</journal-title></journal-title-group><issn pub-type="epub">1932-6203</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, CA USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">25821953</article-id><article-id pub-id-type="pmc">4379102</article-id><article-id pub-id-type="doi">10.1371/journal.pone.0118683</article-id><article-id pub-id-type="publisher-id">PONE-D-14-47833</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title>Lpg0393 of <italic>Legionella pneumophila</italic> Is a Guanine-Nucleotide Exchange Factor for Rab5, Rab21 and Rab22</article-title><alt-title alt-title-type="running-head">Identification of a Bacterial GEF for the Endosomal Rabs</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Sohn</surname><given-names>Young-Sik</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref><xref ref-type="author-notes" rid="econtrib001"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Shin</surname><given-names>Ho-Chul</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref><xref ref-type="aff" rid="aff002"><sup>2</sup></xref><xref ref-type="author-notes" rid="econtrib001"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Park</surname><given-names>Wei Sun</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ge</surname><given-names>Jianning</given-names></name><xref ref-type="aff" rid="aff003"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kim</surname><given-names>Chan-Hee</given-names></name><xref ref-type="aff" rid="aff004"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Lee</surname><given-names>Bok Luel</given-names></name><xref ref-type="aff" rid="aff004"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Do Heo</surname><given-names>Won</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Jung</surname><given-names>Jae U.</given-names></name><xref ref-type="aff" rid="aff003"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Rigden</surname><given-names>Daniel John</given-names></name><xref ref-type="aff" rid="aff005"><sup>5</sup></xref><xref rid="cor001" ref-type="corresp">*</xref></contrib><contrib contrib-type="author"><name><surname>Oh</surname><given-names>Byung-Ha</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref><xref rid="cor001" ref-type="corresp">*</xref></contrib></contrib-group><aff id="aff001"><label>1</label><addr-line>Department of Biological Sciences, KAIST Institute for the Biocentury, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Korea</addr-line></aff><aff id="aff002"><label>2</label><addr-line>Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-600, Korea</addr-line></aff><aff id="aff003"><label>3</label><addr-line>Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America</addr-line></aff><aff id="aff004"><label>4</label><addr-line>Global Research Laboratory of Insect Symbiosis, College of Pharmacy, Pusan National University, Jangjeon Dong, Kumjeong Ku, Busan, 609-735, Korea</addr-line></aff><aff id="aff005"><label>5</label><addr-line>Institute of Integrative Biology, University of Liverpool, Crown St., Liverpool, L69 7ZB, United Kingdom</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Delprato</surname><given-names>Anna Maria</given-names></name><role>Academic Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><addr-line>BioScience Project, UNITED STATES</addr-line></aff><author-notes><fn fn-type="conflict" id="coi001"><p><bold>Competing Interests: </bold>The authors have declared that no competing interests exist.</p></fn><fn fn-type="con" id="contrib001"><p>Conceived and designed the experiments: YSS HCS DJR BHO. Performed the experiments: YSS HCS WSP JG CHK. Analyzed the data: YSS HCS WSP JG CHK WDH JUJ DJR BHO. Contributed reagents/materials/analysis tools: YSS HCS WSP JG CHK BLL WDH JUJ DJR BHO. Wrote the paper: YSS HCS WDH DJR BHO.</p></fn><fn fn-type="other" id="econtrib001"><p>‡ These authors are co-first authors on this work.</p></fn><corresp id="cor001">* E-mail: <email>bhoh@kaist.ac.kr</email> (BHO); <email>drigden@liverpool.ac.uk</email> (DJR)</corresp></author-notes><pub-date pub-type="epub"><day>30</day><month>3</month><year>2015</year></pub-date><pub-date pub-type="collection"><year>2015</year></pub-date><volume>10</volume><issue>3</issue><elocation-id>e0118683</elocation-id><history><date date-type="received"><day>23</day><month>10</month><year>2014</year></date><date date-type="accepted"><day>22</day><month>1</month><year>2015</year></date></history><permissions><copyright-year>2015</copyright-year><copyright-holder>Sohn et al</copyright-holder><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited</license-p></license></permissions><self-uri content-type="pdf" xlink:type="simple" xlink:href="pone.0118683.pdf"></self-uri><abstract><p><italic>Legionella pneumophila</italic>, 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 <italic>Legionella</italic> 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 <italic>Legionella</italic>.</p></abstract><funding-group><funding-statement>This work was supported by the the GRL Program (K20815000001) from National Research Foundation of Korea and by the Intelligent Synthetic Biology Center of Global Frontier Project funded by the Ministry of Education, Science and Technology (No. 2011-0031955). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement></funding-group><counts><fig-count count="5"></fig-count><table-count count="1"></table-count><page-count count="16"></page-count></counts><custom-meta-group><custom-meta id="data-availability"><meta-name>Data Availability</meta-name><meta-value>All relevant data are within the paper.</meta-value></custom-meta></custom-meta-group></article-meta><notes><title>Data Availability</title><p>All relevant data are within the paper.</p></notes></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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