Composition of the type VII secretion system membrane complex
Abstract
Summary: Pathogenic mycobacteria require type VII secretion (T7S) systems to transport virulence factors across their complex cell envelope. These bacteria have up to five of these systems, termed ESX‐1 to ESX‐5. Here, we show that ESX‐5 of M ycobacterium tuberculosis mediates the secretion of EsxN, PPE and PE_PGRS proteins, indicating that ESX‐5 is a major secretion pathway in this important pathogen. Using the ESX‐5 system of M ycobacterium marinum and M ycobacterium bovis BCG as a model, we have purified and analysed the T7S membrane complex under native conditions. blue native‐PAGE and immunoprecipitation experiments showed that the ESX‐5 membrane complex of both species has a size of ∼ 1500 kDa and is composed of four conserved membrane proteins, i.e. EccB 5, EccC 5, EccD 5 and EccE 5. Subsequent limited proteolysis suggests that EccC 5 and EccE 5 mostly reside on the periphery of the complex. We also observed that EccC 5 and EccD 5 expression is essential for the formation of a stable membrane complex. These are the first data on a T7S membrane complex and, given the high conservation of its components, our data can likely be generalized to most mycobacterial T7S systems.
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ESX-5 was suggested to be crucial for nutrient uptake and for the export of members of the PE and PPE protein families.
“ESX-5 was suggested to be crucial for nutrient uptake and for the export of members of the PE and PPE protein families (9,32,33).”
From ESX/Type VII Secretion Systems—An Important Way Out for Mycobacterial Proteins (2019) · cites this paper as [9]
The ESX-5 nanomachine is integrated in the inner mycobacterial membrane and is composed of four proteins, EccB5, EccC5, EccD5, and EccE5, organized in a hexameric complex, as determined by cryo-electron microscopy and single-particle analysis.
“The ESX-5 nanomachine, which is integrated in the inner mycobacterial membrane, is composed of four proteins, namely, EccB5, EccC5, EccD5, and EccE5 (9, 10), that are organized in a hexameric complex, as recently determined by cryoelectron microscopy and single-particle analysis (10).”
From ESX/Type VII Secretion Systems—An Important Way Out for Mycobacterial Proteins (2019) · cites this paper as [9]
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- Authors
- Houben, E. N. G., Bestebroer, J., Ummels, R., Wilson, L., Piersma, S. R., Jiménez, C. R., Ottenhoff, T. H. M., Luirink, J., & Bitter, W.
- Affiliations
- Vrije Universiteit Amsterdam (NL)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Leiden University Medical Center (NL)
- Corresponding author
- Houben, Edith N. G.
- ORCID
- Venue
- Molecular Microbiology
- Publisher
- Wiley
- Published
- 2012-08-27
- Volume
- 86
- Issue
- 2
- Pages
- 472-484
- ISSN
- 0950-382X (ISSN-L)
- 1365-2958
- OpenAlex
- W2151874196
- Cited by
- 168
- References
- 50
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 4 · 2023: 9 · 2022: 5 · 2021: 16 · 2020: 13 · 2019: 21 · 2018: 17 · 2017: 13 · 2016: 20 · 2015: 12 · 2014: 11 · 2013: 12 · 2012: 3
- FWCI
- 8.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- VU Research Portal (submittedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Health Sciences › Medicine › Epidemiology › Mycobacterium research and diagnosis
- Keywords
- type VII secretion system, Mycobacterium tuberculosis, Mycobacterium marinum, Mycobacterium bovis BCG, ECCC, electron cyclotron current drive, ECCE, PPE proteins, PE_PGRS proteins, virulence factor secretion, mycobacterial cell envelope, limited proteolysis
- MeSH terms
- Bacterial Proteins, Cell Membrane, Mycobacterium tuberculosis, Protein Structure, Tertiary, Mycobacterium marinum, Protein Transport, Bacterial Secretion Systems
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