Global atlas of predicted functional domains in Legionella pneumophila Dot/Icm translocated effectors
Abstract Legionella pneumophila utilizes the Dot/Icm type IVB secretion system to deliver hundreds of effector proteins inside eukaryotic cells to ensure intracellular replication. Our understanding of the molecular functions of the largest pathogenic arsenal known to the bacterial world remains inc...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2024-11-01
|
| Series: | Molecular Systems Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s44320-024-00076-z |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841559001577291776 |
|---|---|
| author | Deepak T Patel Peter J Stogios Lukasz Jaroszewski Malene L Urbanus Mayya Sedova Cameron Semper Cathy Le Abraham Takkouche Keita Ichii Julie Innabi Dhruvin H Patel Alexander W Ensminger Adam Godzik Alexei Savchenko |
| author_facet | Deepak T Patel Peter J Stogios Lukasz Jaroszewski Malene L Urbanus Mayya Sedova Cameron Semper Cathy Le Abraham Takkouche Keita Ichii Julie Innabi Dhruvin H Patel Alexander W Ensminger Adam Godzik Alexei Savchenko |
| author_sort | Deepak T Patel |
| collection | DOAJ |
| description | Abstract Legionella pneumophila utilizes the Dot/Icm type IVB secretion system to deliver hundreds of effector proteins inside eukaryotic cells to ensure intracellular replication. Our understanding of the molecular functions of the largest pathogenic arsenal known to the bacterial world remains incomplete. By leveraging advancements in 3D protein structure prediction, we provide a comprehensive structural analysis of 368 L. pneumophila effectors, representing a global atlas of predicted functional domains summarized in a database ( https://pathogens3d.org/legionella-pneumophila ). Our analysis identified 157 types of diverse functional domains in 287 effectors, including 159 effectors with no prior functional annotations. Furthermore, we identified 35 cryptic domains in 30 effector models that have no similarity with experimentally structurally characterized proteins, thus, hinting at novel functionalities. Using this analysis, we demonstrate the activity of thirteen functional domains, including three cryptic domains, predicted in L. pneumophila effectors to cause growth defects in the Saccharomyces cerevisiae model system. This illustrates an emerging strategy of exploring synergies between predictions and targeted experimental approaches in elucidating novel effector activities involved in infection. |
| format | Article |
| id | doaj-art-2445d77116a649b4894b199e4a656e50 |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-2445d77116a649b4894b199e4a656e502025-01-05T12:50:43ZengSpringer NatureMolecular Systems Biology1744-42922024-11-01211598910.1038/s44320-024-00076-zGlobal atlas of predicted functional domains in Legionella pneumophila Dot/Icm translocated effectorsDeepak T Patel0Peter J Stogios1Lukasz Jaroszewski2Malene L Urbanus3Mayya Sedova4Cameron Semper5Cathy Le6Abraham Takkouche7Keita Ichii8Julie Innabi9Dhruvin H Patel10Alexander W Ensminger11Adam Godzik12Alexei Savchenko13Department of Microbiology, Immunology and Infectious Diseases, University of CalgaryBioZone, Department of Chemical Engineering and Applied Chemistry, University of TorontoUniversity of California, Riverside, School of Medicine, Biosciences DivisionDepartment of Biochemistry, University of TorontoUniversity of California, Riverside, School of Medicine, Biosciences DivisionDepartment of Microbiology, Immunology and Infectious Diseases, University of CalgaryDepartment of Microbiology, Immunology and Infectious Diseases, University of CalgaryUniversity of California, Riverside, School of Medicine, Biosciences DivisionUniversity of California, Riverside, School of Medicine, Biosciences DivisionUniversity of California, Riverside, School of Medicine, Biosciences DivisionDepartment of Microbiology, Immunology and Infectious Diseases, University of CalgaryDepartment of Biochemistry, University of TorontoUniversity of California, Riverside, School of Medicine, Biosciences DivisionDepartment of Microbiology, Immunology and Infectious Diseases, University of CalgaryAbstract Legionella pneumophila utilizes the Dot/Icm type IVB secretion system to deliver hundreds of effector proteins inside eukaryotic cells to ensure intracellular replication. Our understanding of the molecular functions of the largest pathogenic arsenal known to the bacterial world remains incomplete. By leveraging advancements in 3D protein structure prediction, we provide a comprehensive structural analysis of 368 L. pneumophila effectors, representing a global atlas of predicted functional domains summarized in a database ( https://pathogens3d.org/legionella-pneumophila ). Our analysis identified 157 types of diverse functional domains in 287 effectors, including 159 effectors with no prior functional annotations. Furthermore, we identified 35 cryptic domains in 30 effector models that have no similarity with experimentally structurally characterized proteins, thus, hinting at novel functionalities. Using this analysis, we demonstrate the activity of thirteen functional domains, including three cryptic domains, predicted in L. pneumophila effectors to cause growth defects in the Saccharomyces cerevisiae model system. This illustrates an emerging strategy of exploring synergies between predictions and targeted experimental approaches in elucidating novel effector activities involved in infection.https://doi.org/10.1038/s44320-024-00076-zBacterial EffectorsLegionella pneumophilaProtein ModelingYeast ToxicityCryptic Domains |
| spellingShingle | Deepak T Patel Peter J Stogios Lukasz Jaroszewski Malene L Urbanus Mayya Sedova Cameron Semper Cathy Le Abraham Takkouche Keita Ichii Julie Innabi Dhruvin H Patel Alexander W Ensminger Adam Godzik Alexei Savchenko Global atlas of predicted functional domains in Legionella pneumophila Dot/Icm translocated effectors Molecular Systems Biology Bacterial Effectors Legionella pneumophila Protein Modeling Yeast Toxicity Cryptic Domains |
| title | Global atlas of predicted functional domains in Legionella pneumophila Dot/Icm translocated effectors |
| title_full | Global atlas of predicted functional domains in Legionella pneumophila Dot/Icm translocated effectors |
| title_fullStr | Global atlas of predicted functional domains in Legionella pneumophila Dot/Icm translocated effectors |
| title_full_unstemmed | Global atlas of predicted functional domains in Legionella pneumophila Dot/Icm translocated effectors |
| title_short | Global atlas of predicted functional domains in Legionella pneumophila Dot/Icm translocated effectors |
| title_sort | global atlas of predicted functional domains in legionella pneumophila dot icm translocated effectors |
| topic | Bacterial Effectors Legionella pneumophila Protein Modeling Yeast Toxicity Cryptic Domains |
| url | https://doi.org/10.1038/s44320-024-00076-z |
| work_keys_str_mv | AT deepaktpatel globalatlasofpredictedfunctionaldomainsinlegionellapneumophiladoticmtranslocatedeffectors AT peterjstogios globalatlasofpredictedfunctionaldomainsinlegionellapneumophiladoticmtranslocatedeffectors AT lukaszjaroszewski globalatlasofpredictedfunctionaldomainsinlegionellapneumophiladoticmtranslocatedeffectors AT malenelurbanus globalatlasofpredictedfunctionaldomainsinlegionellapneumophiladoticmtranslocatedeffectors AT mayyasedova globalatlasofpredictedfunctionaldomainsinlegionellapneumophiladoticmtranslocatedeffectors AT cameronsemper globalatlasofpredictedfunctionaldomainsinlegionellapneumophiladoticmtranslocatedeffectors AT cathyle globalatlasofpredictedfunctionaldomainsinlegionellapneumophiladoticmtranslocatedeffectors AT abrahamtakkouche globalatlasofpredictedfunctionaldomainsinlegionellapneumophiladoticmtranslocatedeffectors AT keitaichii globalatlasofpredictedfunctionaldomainsinlegionellapneumophiladoticmtranslocatedeffectors AT julieinnabi globalatlasofpredictedfunctionaldomainsinlegionellapneumophiladoticmtranslocatedeffectors AT dhruvinhpatel globalatlasofpredictedfunctionaldomainsinlegionellapneumophiladoticmtranslocatedeffectors AT alexanderwensminger globalatlasofpredictedfunctionaldomainsinlegionellapneumophiladoticmtranslocatedeffectors AT adamgodzik globalatlasofpredictedfunctionaldomainsinlegionellapneumophiladoticmtranslocatedeffectors AT alexeisavchenko globalatlasofpredictedfunctionaldomainsinlegionellapneumophiladoticmtranslocatedeffectors |