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Modification of a PE/PPE substrate pair reroutes an Esx substrate pair from the mycobacterial ESX-1 type VII secretion system to the ESX-5 system.
- Source :
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The Journal of biological chemistry [J Biol Chem] 2020 May 01; Vol. 295 (18), pp. 5960-5969. Date of Electronic Publication: 2020 Mar 17. - Publication Year :
- 2020
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Abstract
- Bacterial type VII secretion systems secrete a wide range of extracellular proteins that play important roles in bacterial viability and in interactions of pathogenic mycobacteria with their hosts. Mycobacterial type VII secretion systems consist of five subtypes, ESX-1-5, and have four substrate classes, namely, Esx, PE, PPE, and Esp proteins. At least some of these substrates are secreted as heterodimers. Each ESX system mediates the secretion of a specific set of Esx, PE, and PPE proteins, raising the question of how these substrates are recognized in a system-specific fashion. For the PE/PPE heterodimers, it has been shown that they interact with their cognate EspG chaperone and that this chaperone determines the designated secretion pathway. However, both structural and pulldown analyses have suggested that EspG cannot interact with the Esx proteins. Therefore, the determining factor for system specificity of the Esx proteins remains unknown. Here, we investigated the secretion specificity of the ESX-1 substrate pair EsxB&#95;1/EsxA&#95;1 in Mycobacterium marinum Although this substrate pair was hardly secreted when homologously expressed, it was secreted when co-expressed together with the PE35/PPE68&#95;1 pair, indicating that this pair could stimulate secretion of the EsxB&#95;1/EsxA&#95;1 pair. Surprisingly, co-expression of EsxB&#95;1/EsxA&#95;1 with a modified PE35/PPE68&#95;1 version that carried the EspG <subscript>5</subscript> chaperone-binding domain, previously shown to redirect this substrate pair to the ESX-5 system, also resulted in redirection and co-secretion of the Esx pair via ESX-5. Our results suggest a secretion model in which PE35/PPE68&#95;1 determines the system-specific secretion of EsxB&#95;1/EsxA&#95;1.<br /> (© 2020 Damen et al.)
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 295
- Issue :
- 18
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 32184351
- Full Text :
- https://doi.org/10.1074/jbc.RA119.011682