Structural insight into the distinct regulatory mechanism of the HEPN–MNT toxin-antitoxin system in Legionella pneumophila

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.

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Publication Details

Journal
Nature Communications
Published
2024-11-24
DOI
https://doi.org/10.1038/s41467-024-54551-0
Citations
1
Primary Topic
Legionella and Acanthamoeba research
Type
article
Field-Weighted Citation Impact
0.62

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article

Structural insight into the distinct regulatory mechanism of the HEPN–MNT toxin-antitoxin system in Legionella pneumophila

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Legionella and Acanthamoeba research
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article

Structural insight into the distinct regulatory mechanism of the HEPN–MNT toxin-antitoxin system in Legionella pneumophila

Byung Woo Han, Do‐Hee Kim, Jin Kang, Chan-Woo Jeon, Yuri Choi, Chenglong Jin, Sung‐Min Kang, Bong‐Jin Lee, Hyung Ho Lee, Heoung-yeol Kim
article en
1 citations

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.

Nature CommunicationsVol. 15(1)
Seoul National University (KR), Sookmyung Women's University (KR), Boditech Med (South Korea) (KR), National University College (PR), Ajou University (KR), Duksung Women's University (KR)
National Research Foundation, Mokpo National University, National Research Foundation of Korea, Institute for Protein Research, Osaka University
Openalex Percentile: Top 26%
Legionella and Acanthamoeba research
0.62
DOIOpen Access PDFOpenAlex
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