Structural insight into the distinct regulatory mechanism of the HEPN–MNT toxin-antitoxin system in Legionella pneumophila
Abstract HEPN–MNT, a type VII TA module, comprises the HEPN toxin and the MNT antitoxin, which acts as a nucleotidyltransferase that transfers the NMP moiety to the corresponding HEPN toxin, thereby interfering with its toxicity. Here, we report crystal structures of the Legionella pneumophila HEPN–...
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Nature Portfolio
2024-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54551-0 |
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| author | Chenglong Jin Cha-Hee Jeon Heung Wan Kim Jin Mo Kang Yuri Choi Sung-Min Kang Hyung Ho Lee Do-Hee Kim Byung Woo Han Bong-Jin Lee |
| author_facet | Chenglong Jin Cha-Hee Jeon Heung Wan Kim Jin Mo Kang Yuri Choi Sung-Min Kang Hyung Ho Lee Do-Hee Kim Byung Woo Han Bong-Jin Lee |
| author_sort | Chenglong Jin |
| collection | DOAJ |
| description | Abstract HEPN–MNT, a type VII TA module, comprises the HEPN toxin and the MNT antitoxin, which acts as a nucleotidyltransferase that transfers the NMP moiety to the corresponding HEPN toxin, thereby interfering with its toxicity. Here, we report crystal structures of the Legionella pneumophila HEPN–MNT module, including HEPN, AMPylated HEPN, MNT, and the HEPN–MNT complex. Our structural analysis and biochemical assays, suggest that HEPN is a metal-dependent RNase and identify its active site residues. We also elucidate the oligomeric state of HEPN in solution. Interestingly, L. pneumophila MNT, which lacks a long C-terminal α4 helix, controls the toxicity of HEPN toxin via a distinct binding mode with HEPN. Finally, we propose a comprehensive regulatory mechanism of the L. pneumophila HEPN–MNT module based on structural and functional studies. These results provide insight into the type VII HEPN–MNT TA system. |
| format | Article |
| id | doaj-art-d2090d749b58491a99ff2b59661cdebb |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-d2090d749b58491a99ff2b59661cdebb2024-11-24T12:32:08ZengNature PortfolioNature Communications2041-17232024-11-0115111610.1038/s41467-024-54551-0Structural insight into the distinct regulatory mechanism of the HEPN–MNT toxin-antitoxin system in Legionella pneumophilaChenglong Jin0Cha-Hee Jeon1Heung Wan Kim2Jin Mo Kang3Yuri Choi4Sung-Min Kang5Hyung Ho Lee6Do-Hee Kim7Byung Woo Han8Bong-Jin Lee9The Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National UniversityThe Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National UniversityThe Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National UniversityThe Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National UniversityDepartment of Chemistry, College of Natural Sciences, Seoul National UniversityCollege of Pharmacy, Duksung Women’s UniversityDepartment of Chemistry, College of Natural Sciences, Seoul National UniversityResearch Institute of Pharmaceutical Sciences, College of Pharmacy, Sookmyung Women’s UniversityThe Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National UniversityMasterMediTechAbstract HEPN–MNT, a type VII TA module, comprises the HEPN toxin and the MNT antitoxin, which acts as a nucleotidyltransferase that transfers the NMP moiety to the corresponding HEPN toxin, thereby interfering with its toxicity. Here, we report crystal structures of the Legionella pneumophila HEPN–MNT module, including HEPN, AMPylated HEPN, MNT, and the HEPN–MNT complex. Our structural analysis and biochemical assays, suggest that HEPN is a metal-dependent RNase and identify its active site residues. We also elucidate the oligomeric state of HEPN in solution. Interestingly, L. pneumophila MNT, which lacks a long C-terminal α4 helix, controls the toxicity of HEPN toxin via a distinct binding mode with HEPN. Finally, we propose a comprehensive regulatory mechanism of the L. pneumophila HEPN–MNT module based on structural and functional studies. These results provide insight into the type VII HEPN–MNT TA system.https://doi.org/10.1038/s41467-024-54551-0 |
| spellingShingle | Chenglong Jin Cha-Hee Jeon Heung Wan Kim Jin Mo Kang Yuri Choi Sung-Min Kang Hyung Ho Lee Do-Hee Kim Byung Woo Han Bong-Jin Lee Structural insight into the distinct regulatory mechanism of the HEPN–MNT toxin-antitoxin system in Legionella pneumophila Nature Communications |
| title | Structural insight into the distinct regulatory mechanism of the HEPN–MNT toxin-antitoxin system in Legionella pneumophila |
| title_full | Structural insight into the distinct regulatory mechanism of the HEPN–MNT toxin-antitoxin system in Legionella pneumophila |
| title_fullStr | Structural insight into the distinct regulatory mechanism of the HEPN–MNT toxin-antitoxin system in Legionella pneumophila |
| title_full_unstemmed | Structural insight into the distinct regulatory mechanism of the HEPN–MNT toxin-antitoxin system in Legionella pneumophila |
| title_short | Structural insight into the distinct regulatory mechanism of the HEPN–MNT toxin-antitoxin system in Legionella pneumophila |
| title_sort | structural insight into the distinct regulatory mechanism of the hepn mnt toxin antitoxin system in legionella pneumophila |
| url | https://doi.org/10.1038/s41467-024-54551-0 |
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