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Three small partner proteins facilitate the type VII-dependent secretion of an antibacterial nuclease

Lookup NU author(s): Yaping Yang, Ellie Boardman, Dr Felicity AlcockORCiD, Professor Tracy Palmer FRS FRSE FMedSciORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2023 Yang et al. The type VIIb secretion system (T7SSb) is a multisubunit protein export machine found in Gram-positive Bacillota which plays a key role in interbacterial competition. The T7SSb secretes a variety of toxic effectorproteins targeting closely related strains; however, 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 pre-secretion complex with its cognate immunity protein, EsaG, and chaperone EsaE. Encoded upstream of EsaD are three small secreted proteins of unknown function: EsxB, EsxC, and EsxD. Here, we show that these three proteins bind to EsaD and function as EsaD export factors and we report preliminary structural information for a complete T7SSb substrate pre-secretion complex. Cryo-electron microscopy of the EsaDEG trimer and the EsaDEG-EsxBCD hexamer shows that incorporation of EsxBCD confers an elongated conformation comprising a flexibleglobular cargo domain attached to a long narrow shaft that is likely to be crucial for efficienttoxin export.


Publication metadata

Author(s): Yang Y, Boardman E, Deme J, Alcock F, Lea S, Palmer T

Publication type: Article

Publication status: Published

Journal: mBio

Year: 2023

Volume: 14

Issue: 5

Online publication date: 10/10/2023

Acceptance date: 23/08/2023

Date deposited: 25/01/2024

ISSN (print): 2161-2129

ISSN (electronic): 2150-7511

Publisher: American Society for Microbiology

URL: https://doi.org/10.1128/mbio.02100-23

DOI: 10.1128/mbio.02100-23

PubMed id: 37815362


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Funding

Funder referenceFunder name
10183/Z/15/Z
224151/Z/21/Z
China Scholarship Council
Intramural Research Program of the NIH, NCI, Center for Cancer Research
University of Newcastle
Wellcome Trust

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