Species-specific secretion of ESX-5 type VII substrates is determined by the linker 2 of EccC5
| Autor: | Catalin M. Bunduc, Wilbert Bitter, Edith N.G. Houben, Roy Ummels |
|---|---|
| Přispěvatelé: | Medical Microbiology and Infection Prevention, AII - Infectious diseases, Molecular Microbiology, AIMMS |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Virulence Factors
substrate specificity Mutant Virulence Microbiology mycobacterium Mycobacterium tuberculosis 03 medical and health sciences Bacterial Proteins Protein Domains Species Specificity membrane ATPase SDG 3 - Good Health and Well-being Secretion SDG 14 - Life Below Water chimeras Molecular Biology Pathogen Research Articles Mycobacterium marinum 030304 developmental biology Adenosine Triphosphatases 0303 health sciences biology Chimera Effector Chemistry 030306 microbiology ESX Cell Membrane type VII secretion biology.organism_classification Cell biology Biochemistry Type VII Secretion Systems Cell envelope Linker Research Article Mycobacterium |
| Zdroj: | Molecular Microbiology, 114(1), 66-76. Wiley-Blackwell Bunduc, C M, Ummels, R, Bitter, W & Houben, E N G 2020, ' Species-specific secretion of ESX-5 type VII substrates is determined by the linker 2 of EccC 5 ', Molecular Microbiology, vol. 114, no. 1, pp. 66-76 . https://doi.org/10.1111/mmi.14496 Bunduc, C M, Ummels, R, Bitter, W & Houben, E N G 2020, ' Species-specific secretion of ESX-5 type VII substrates is determined by the linker 2 of EccC5 ', Molecular Microbiology, vol. 114, no. 1, pp. 66-76 . https://doi.org/10.1111/mmi.14496 Molecular Microbiology |
| ISSN: | 0950-382X |
| Popis: | Mycobacteria use type VII secretion systems (T7SSs) to translocate a wide range of proteins across their diderm cell envelope. These systems, also called ESX systems, are crucial for the viability and/or virulence of mycobacterial pathogens, including Mycobacterium tuberculosis and the fish pathogen Mycobacterium marinum. We have previously shown that the M. tuberculosis ESX‐5 system is unable to fully complement secretion in an M. marinum esx‐5 mutant, suggesting species specificity in secretion. In this study, we elaborated on this observation and established that the membrane ATPase EccC5, possessing four (putative) nucleotide‐binding domains (NBDs), is responsible for this. By creating M. marinum‐M. tuberculosis EccC5 chimeras, we observed both in M. marinum and in M. tuberculosis that secretion specificity of PE_PGRS proteins depends on the presence of the cognate linker 2 domain of EccC5. This region connects NBD1 and NBD2 of EccC5 and is responsible for keeping NBD1 in an inhibited state. Notably, the ESX‐5 substrate EsxN, predicted to bind to NBD3 on EccC5, showed a distinct secretion profile. These results indicate that linker 2 is involved in species‐specific substrate recognition and might therefore be an additional substrate recognition site of EccC5. One of the major virulence factors of Mycobacterium tuberculosis and other pathogenic mycobacteria are the type VII secretion systems. Here, we provide an important insight into the mechanism of substrate recognition by these systems by identifying a putative second substrate recognition site on the central type VII secretion membrane ATPase EccC. |
| Databáze: | OpenAIRE |
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