8QHC

Cryo-EM structure of SidH from Legionella pneumophila in complex with LubX

Summary for 8QHC

• Entry DOI: 10.2210/pdb8qhc/pdb
• Related: 8QFS
• EMDB information: 18383 18407
• Descriptor: Elongation factor Tu, t-RNA, Protein SidH, ... (6 entities in total)
• Functional Keywords: sidh, legionella, trna-binding, ef-tu-binding, rna binding protein
• Biological source: Legionella pneumophila; More
• Total number of polymer chains: 4
• Total formula weight: 354159.29

Authors

Sharma, R.,Adams, M.,Bhogaraju, S. (deposition date: 2023-09-07, release date: 2023-10-11, Last modification date: 2023-11-15)

Primary citation

Sharma, R.,Adams, M.,Griffith-Jones, S.,Sahr, T.,Gomez-Valero, L.,Weis, F.,Hons, M.,Gharbi, S.,Berkane, R.,Stolz, A.,Buchrieser, C.,Bhogaraju, S.
Structural basis for the toxicity of Legionella pneumophila effector SidH.
Nat Commun, 14:7068-7068, 2023

PubMed Abstract: 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.

PubMed: 37923743
DOI: 10.1038/s41467-023-42683-8

Experimental method

ELECTRON MICROSCOPY (3.1 Å)