ArticleProceedings of the National Academy of Sciences of the United States of America2012
General secretion signal for the mycobacterial type VII secretion pathway.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers.
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122 citing papers in PubMed, 198 citations in OpenAlex.
- Type VIIb secretion systems in Lactobacillales: insights from streptococci and enterococci.Journal of bacteriology · 2026Review
- Multiple aspartic proteases process PE and PPE proteins on the mycobacterial surface of pathogenic mycobacteria.The Journal of biological chemistry · 2026Article
- EsxA is required for antibacterial toxin export by the type VIIb secretion system.The Journal of biological chemistry · 2026Article
- A Type VII-secreted toxin enables inter-mycobacterial competition.Nature communications · 2026Article
- Review
- Harnessing toxin-mediated ribosome stalling as a complementary tool to annotate bacterial ORFs.Nucleic acids research · 2026Article
- Sigma factor M induces an ESX-4-focused regulon inFrontiers in tuberculosis · 2026Article
- Control of Mycobacterium tuberculosis protein secretion by ESX-4 and the outer membrane EsxUT-EsxEF complex.Nature communications · 2025Article
- Article
- PPE51 modulates membrane integrity inmBio · 2025Article
- Characterization of PPE19 as a novel mediator ofmSphere · 2025Article
- A LXG toxin stabilized by DUF4176 contributes to Streptococcus suis competition and pathogenicity.BMC biology · 2025Article
- PPE50 variants as novel phylogeographic signatures of host-pathogen co-evolution in tuberculosis.Communications biology · 2025Article
- The PE/PPE family proteins ofFrontiers in immunology · 2025Review
- Identifying a type of toxic effectors exported by the type VII secretion system to enhance competitive fitness inFrontiers in cellular and infection microbiology · 2025Article
- PE/PPE Proteome and ESX-5 Substrate Spectrum inInternational journal of molecular sciences · 2024Article
- New insights into the domain of unknown function (DUF) of EccCActa crystallographica. Section D, Structural biology · 2024Article
- Live Attenuated Vaccines against Tuberculosis: Targeting the Disruption of Genes Encoding the Secretory Proteins of Mycobacteria.Vaccines · 2024Review
- Proteomics from compartment-specific APEX2 labeling in Mycobacterium tuberculosis reveals Type VII secretion substrates in the cell wall.Cell chemical biology · 2024Article
- Structure of a tripartite protein complex that targets toxins to the type VII secretion system.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
62 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mycobacterial pathogens use specialized type VII secretion (T7S) systems to transport crucial virulence factors across their unusual cell envelope into infected host cells. These virulence factors lack classical secretion signals and the mechanism of substrate recognition is not well understood. Here we demonstrate that the model T7S substrates PE25/PPE41, which form a heterodimer, are targeted to the T7S pathway ESX-5 by a signal located in the C terminus of PE25. Site-directed mutagenesis of residues within this C terminus resulted in the identification of a highly conserved motif, i.e., YxxxD/E, which is required for secretion. This motif was also essential for the secretion of LipY, another ESX-5 substrate. Pathogenic mycobacteria have several different T7S systems and we identified a PE protein that is secreted by the ESX-1 system, which allowed us to compare substrate recognition of these two T7S systems. Surprisingly, this ESX-1 substrate contained a C-terminal signal functionally equivalent to that of PE25. Exchange of these C-terminal secretion signals between the PE proteins restored secretion, but each PE protein remained secreted via its own ESX secretion system, indicating that an additional signal(s) provides system specificity. Remarkably, the YxxxD/E motif was also present in and required for efficient secretion of the ESX-1 substrates CFP-10 and EspB. Therefore, our data show that the YxxxD/E motif is a general secretion signal that is present in all known mycobacterial T7S substrates or substrate complexes.
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