Structure of the Virulence Factor, SidC Reveals a Unique PI(4)P-Specific Binding Domain Essential for Its Targeting to the Bacterial Phagosome

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Legionnaires’ disease is caused by the intracellular bacterial pathogen Legionella pneumophila. Successful infection by this bacterium requires a special secretion system that injects nearly 300 effector proteins into the cytoplasm of host cells. The effector SidC and its paralog SdcA anchor on the Legionella-containing vacuole (LCV) and are important for the recruitment of ER proteins to the LCV. Recent data demonstrated that SidC and SdcA are ubiquitin E3 ligases and that their activity is required for the enrichment of ER proteins and ubiquitin conjugates on the LCV. Here we present the crystal structure of SidC revealing the architecture of a novel PI(4)P-binding module. Our biochemical and cell biological studies highlight key determinants involved in PI(4)P-binding and membrane insertion. Characterization of this novel PI(4)P binding module opens a potential avenue for the development of an accurate in vivo PI(4)P probe. Our data also reveals a distinct regulatory mechanism of the ubiquitin E3 ligase activity of SidC, which is activated by the lipid molecule, PI(4)P. Furthermore, our results suggest that proper spatial localization of SidC to the cytoplasmic surface of the bacterial phagosome through the binding with PI(4)P is crucial to its function.

Vyšlo v časopise: Structure of the Virulence Factor, SidC Reveals a Unique PI(4)P-Specific Binding Domain Essential for Its Targeting to the Bacterial Phagosome. PLoS Pathog 11(6): e32767. doi:10.1371/journal.ppat.1004965
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004965

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