ArticleProceedings of the National Academy of Sciences of the United States of America2013
Computational modeling and experimental validation of the Legionella and Coxiella virulence-related type-IVB secretion signal.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.
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Who cites it
117 citing papers in PubMed.
- Article
- The Legionella pneumophila type IVb secretion system effector BinA subverts amino acid transport to sensitize TORC1 signaling in macrophages.PLoS pathogens · 2026Article
- Transmembrane effector substrates of type IV secretion systems: mechanisms of secretion and insertion into host cell membranes.microLife · 2026Review
- Molecular evolution and adaptations ofFrontiers in cellular and infection microbiology · 2026Review
- Systematic Discovery of Pathogen Effector Functions across Human Pathogens and Pathways.bioRxiv : the preprint server for biology · 2025Article
- A diverse family of bacterial deubiquitinases is defined by theProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Legionella effector LpPIP recruits protein phosphatase 1 to the mitochondria to induce dephosphorylation of outer membrane proteins.PLoS biology · 2025Article
- Identification of aInfection and immunity · 2025Article
- IL-1beta expressing neutrophil extracellular traps inFrontiers in immunology · 2025Article
- Review
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- CRISPRi functional genomics in bacteria and its application to medical and industrial research.Microbiology and molecular biology reviews : MMBR · 2024Review
- The multifunctionProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Ecology ofBiofilm · 2024Review
- Coxiella burnetii protein CBU2016 supports CCV expansion.Pathogens and disease · 2024Article
- Protein Sorting Prediction.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Article
- The Sde phosphoribosyl-linked ubiquitin transferases protect theProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Macrophage infectivity potentiator protein, a peptidyl prolyl cis-trans isomerase, essential for Coxiella burnetii growth and pathogenesis.PLoS pathogens · 2023Article
57 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors.
Funding
Abstract
Legionella and Coxiella are intracellular pathogens that use the virulence-related Icm/Dot type-IVB secretion system to translocate effector proteins into host cells during infection. These effectors were previously shown to contain a C-terminal secretion signal required for their translocation. In this research, we implemented a hidden semi-Markov model to characterize the amino acid composition of the signal, thus providing a comprehensive computational model for the secretion signal. This model accounts for dependencies among sites and captures spatial variation in amino acid composition along the secretion signal. To validate our model, we predicted and synthetically constructed an optimal secretion signal whose sequence is different from that of any known effector. We show that this signal efficiently translocates into host cells in an Icm/Dot-dependent manner. Additionally, we predicted in silico and experimentally examined the effects of mutations in the secretion signal, which provided innovative insights into its characteristics. Some effectors were found to lack a strong secretion signal according to our model. We demonstrated that these effectors were highly dependent on the IcmS-IcmW chaperons for their translocation, unlike effectors that harbor a strong secretion signal. Furthermore, our model is innovative because it enables searching ORFs for secretion signals on a genomic scale, which led to the identification and experimental validation of 20 effectors from Legionella pneumophila, Legionella longbeachae, and Coxiella burnetii. Our combined computational and experimental methodology is general and can be applied to the identification of a wide spectrum of protein features that lack sequence conservation but have similar amino acid characteristics.
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