8QHC

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

8QHC の概要

• エントリーDOI: 10.2210/pdb8qhc/pdb
• 関連するPDBエントリー: 8QFS
• EMDBエントリー: 18383 18407
• 分子名称: Elongation factor Tu, t-RNA, Protein SidH, ... (6 entities in total)
• 機能のキーワード: sidh, legionella, trna-binding, ef-tu-binding, rna binding protein
• 由来する生物種: Legionella pneumophila; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 354159.29

構造登録者

Sharma, R.,Adams, M.,Bhogaraju, S. (登録日: 2023-09-07, 公開日: 2023-10-11, 最終更新日: 2023-11-15)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.1 Å)