Discovery of Ubiquitin Deamidases in the Pathogenic Arsenal of Legionella pneumophila
Summary: Legionella pneumophila translocates the largest known arsenal of over 330 pathogenic factors, called “effectors,” into host cells during infection, enabling L. pneumophila to establish a replicative niche inside diverse amebas and human macrophages. Here, we reveal that the L. pneumophila e...
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2018-04-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718304054 |
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doaj-4a5302e8183f41a78230f4eb340185042020-11-24T21:36:16ZengElsevierCell Reports2211-12472018-04-01232568583Discovery of Ubiquitin Deamidases in the Pathogenic Arsenal of Legionella pneumophilaDylan Valleau0Andrew T. Quaile1Hong Cui2Xiaohui Xu3Elena Evdokimova4Changsoo Chang5Marianne E. Cuff6Malene L. Urbanus7Scott Houliston8Cheryl H. Arrowsmith9Alexander W. Ensminger10Alexei Savchenko11Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON, CanadaDepartment of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON, CanadaThe Hospital for Sick Children Research Institute and Department of Biochemistry, University of Toronto, Toronto, ON, CanadaDepartment of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON, CanadaDepartment of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON, CanadaStructural Biology Center, Biosciences Division, Argonne National Laboratory, Argonne, IL, USAStructural Biology Center, Biosciences Division, Argonne National Laboratory, Argonne, IL, USADepartment of Biochemistry, University of Toronto, Toronto, ON, CanadaStructural Genomics Consortium, University of Toronto, Toronto, ON, Canada; Princess Margaret Cancer Centre and Department of Medical Biophysics, University of Toronto, Toronto, ON, CanadaStructural Genomics Consortium, University of Toronto, Toronto, ON, Canada; Princess Margaret Cancer Centre and Department of Medical Biophysics, University of Toronto, Toronto, ON, CanadaDepartment of Biochemistry, University of Toronto, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, CanadaDepartment of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON, Canada; Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, AB, Canada; Corresponding authorSummary: Legionella pneumophila translocates the largest known arsenal of over 330 pathogenic factors, called “effectors,” into host cells during infection, enabling L. pneumophila to establish a replicative niche inside diverse amebas and human macrophages. Here, we reveal that the L. pneumophila effectors MavC (Lpg2147) and MvcA (Lpg2148) are structural homologs of cycle inhibiting factor (Cif) effectors and that the adjacent gene, lpg2149, produces a protein that directly inhibits their activity. In contrast to canonical Cifs, both MavC and MvcA contain an insertion domain and deamidate the residue Gln40 of ubiquitin but not Gln40 of NEDD8. MavC and MvcA are functionally diverse, with only MavC interacting with the human E2-conjugating enzyme UBE2N (Ubc13). MavC deamidates the UBE2N∼Ub conjugate, disrupting Lys63 ubiquitination and dampening NF-κB signaling. Combined, our data reveal a molecular mechanism of host manipulation by pathogenic bacteria and highlight the complex regulatory mechanisms integral to L. pneumophila’s pathogenic strategy. : Legionella pneumophila, possessing the largest known arsenal of effectors, continues to reveal unique approaches to host cell control. Valleau et al. decrypt the functions of a trio of effectors, discovering a pair of ubiquitin-specific deamidases, their regulation by a neighboring dual-specificity protein inhibitor, and a mechanism of NF-κB suppression. Keywords: pathogen-host interaction, ubiquitination, Legionella, UBE2N/Ubc13, NF-κB signaling, Type IV secretion system, effectors, metaeffector, cycle inhibiting factorhttp://www.sciencedirect.com/science/article/pii/S2211124718304054 |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Dylan Valleau Andrew T. Quaile Hong Cui Xiaohui Xu Elena Evdokimova Changsoo Chang Marianne E. Cuff Malene L. Urbanus Scott Houliston Cheryl H. Arrowsmith Alexander W. Ensminger Alexei Savchenko |
| spellingShingle |
Dylan Valleau Andrew T. Quaile Hong Cui Xiaohui Xu Elena Evdokimova Changsoo Chang Marianne E. Cuff Malene L. Urbanus Scott Houliston Cheryl H. Arrowsmith Alexander W. Ensminger Alexei Savchenko Discovery of Ubiquitin Deamidases in the Pathogenic Arsenal of Legionella pneumophila Cell Reports |
| author_facet |
Dylan Valleau Andrew T. Quaile Hong Cui Xiaohui Xu Elena Evdokimova Changsoo Chang Marianne E. Cuff Malene L. Urbanus Scott Houliston Cheryl H. Arrowsmith Alexander W. Ensminger Alexei Savchenko |
| author_sort |
Dylan Valleau |
| title |
Discovery of Ubiquitin Deamidases in the Pathogenic Arsenal of Legionella pneumophila |
| title_short |
Discovery of Ubiquitin Deamidases in the Pathogenic Arsenal of Legionella pneumophila |
| title_full |
Discovery of Ubiquitin Deamidases in the Pathogenic Arsenal of Legionella pneumophila |
| title_fullStr |
Discovery of Ubiquitin Deamidases in the Pathogenic Arsenal of Legionella pneumophila |
| title_full_unstemmed |
Discovery of Ubiquitin Deamidases in the Pathogenic Arsenal of Legionella pneumophila |
| title_sort |
discovery of ubiquitin deamidases in the pathogenic arsenal of legionella pneumophila |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2018-04-01 |
| description |
Summary: Legionella pneumophila translocates the largest known arsenal of over 330 pathogenic factors, called “effectors,” into host cells during infection, enabling L. pneumophila to establish a replicative niche inside diverse amebas and human macrophages. Here, we reveal that the L. pneumophila effectors MavC (Lpg2147) and MvcA (Lpg2148) are structural homologs of cycle inhibiting factor (Cif) effectors and that the adjacent gene, lpg2149, produces a protein that directly inhibits their activity. In contrast to canonical Cifs, both MavC and MvcA contain an insertion domain and deamidate the residue Gln40 of ubiquitin but not Gln40 of NEDD8. MavC and MvcA are functionally diverse, with only MavC interacting with the human E2-conjugating enzyme UBE2N (Ubc13). MavC deamidates the UBE2N∼Ub conjugate, disrupting Lys63 ubiquitination and dampening NF-κB signaling. Combined, our data reveal a molecular mechanism of host manipulation by pathogenic bacteria and highlight the complex regulatory mechanisms integral to L. pneumophila’s pathogenic strategy. : Legionella pneumophila, possessing the largest known arsenal of effectors, continues to reveal unique approaches to host cell control. Valleau et al. decrypt the functions of a trio of effectors, discovering a pair of ubiquitin-specific deamidases, their regulation by a neighboring dual-specificity protein inhibitor, and a mechanism of NF-κB suppression. Keywords: pathogen-host interaction, ubiquitination, Legionella, UBE2N/Ubc13, NF-κB signaling, Type IV secretion system, effectors, metaeffector, cycle inhibiting factor |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124718304054 |
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