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Article Dans Une Revue Nature Communications Année : 2023

Structural basis for the toxicity of Legionella pneumophila effector SidH

Rayene Berkane
Alexandra Stolz

Résumé

Legionella pneumophila ( LP ) secretes more than 300 effectors into the host cytosol to facilitate intracellular replication. One of these effectors, SidH, 253 kDa in size with no sequence similarity to proteins of known function is toxic when overexpressed in host cells. SidH is regulated by the LP metaeffector LubX which targets SidH for degradation in a temporal manner during LP infection. The mechanism underlying the toxicity of SidH and its role in LP infection are unknown. Here, we determined the cryo-EM structure of SidH at 2.7 Å revealing a unique alpha helical arrangement with no overall similarity to known protein structures. Surprisingly, purified SidH came bound to a E. coli EF-Tu/t-RNA/GTP ternary complex which could be modeled into the cryo-EM density. Mutation of residues disrupting the SidH-tRNA interface and SidH-EF-Tu interface abolish the toxicity of overexpressed SidH in human cells, a phenotype confirmed in infection of Acanthamoeba castellani . We also present the cryo-EM structure of SidH in complex with a U-box domain containing ubiquitin ligase LubX delineating the mechanism of regulation of SidH. Our data provide the basis for the toxicity of SidH and into its regulation by the metaeffector LubX.
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hal-04636160 , version 1 (23-07-2024)

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Rahul Sharma, Michael Adams, Simonne Griffith-Jones, Tobias Sahr, Laura Gomez-Valero, et al.. Structural basis for the toxicity of Legionella pneumophila effector SidH. Nature Communications, 2023, 14 (1), pp.7068. ⟨10.1038/s41467-023-42683-8⟩. ⟨hal-04636160⟩
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