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Three small partner proteins facilitate the type VII-dependent secretion export of an antibacterial nuclease
Open accessPreprint — published as 10.1128/mbio.02100-23 · Paper page
Abstract
Summary: The type VIIb protein secretion system (T7SSb) plays a role in interbacterial competition in Gram-positive Firmicute bacteria and secretes various toxic effector proteins. The mechanism of secretion and the roles of numerous conserved genes within T7SSb gene clusters remain unknown. EsaD is a nuclease toxin secreted by the Staphylococcus aureus T7SSb, which forms a complex with its cognate immunity protein, EsaG, and chaperone EsaE. Encoded upstream of EsaD are three small secreted proteins, EsxB, EsxC and EsxD. Here we show that EsxBCD bind to the transport domain of EsaD and function as EsaD export factors. We report the first structural information for a complete T7SSb substrate pre-secretion complex. Cryo-EM of the EsaDEG trimer and the EsaDEG-EsxBCD hexamer shows that incorporation of EsxBCD confers a conformation comprising a flexible globular cargo domain attached to a long narrow shaft that is likely to be crucial for efficient toxin export.
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Metadata
- Authors
- Yang, Y., Boardman, E., Deme, J., Alcock, F., Lea, S., & Palmer, T.
- Affiliations
- Newcastle University (GB)
- National Institutes of Health (US)
- Corresponding author
- Palmer, Tracy
- Venue
- mBio
- Publisher
- openRxiv
- Published
- 2023-04-01
- Volume
- 14
- Issue
- 5
- Pages
- e0210023-e0210023
- ISSN
- 2150-7511 (ISSN-L)
- PMC
- PMC10653861
- OpenAlex
- W4387472287
- Cited by
- 27
- References
- 1
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 9 · 2023: 5
- FWCI
- 5.56
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- mBio (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Newcastle University ePrints (Newcastle Univesity) (cc-by)
- Funders
- Wellcome Trust (224151/Z/21/Z, 224151, /Z/15/Z, 10183/Z/15/Z)
- China Scholarship Council
- National Institutes of Health
- National Cancer Institute
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
- Keywords
- type VII secretion system, Staphylococcus aureus, CFP-10, export determinants, bacterial competition
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