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Lookup NU author(s): Stephen Garrett, Dr Nicole Mietrach, Yaping Yang, Dr Fatima Ulhuq, Professor Tracy Palmer FRS FRSE FMedSciORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2023, The Author(s). The type VII protein secretion system (T7SS) is found in many Gram-positive bacteria and in pathogenic mycobacteria. All T7SS substrate proteins described to date share a common helical domain architecture at the N-terminus that typically interacts with other helical partner proteins, forming a composite signal sequence for targeting to the T7SS. The C-terminal domains are functionally diverse and in Gram-positive bacteria such as Staphylococcus aureus often specify toxic anti-bacterial activity. Here we describe the first example of a class of T7 substrate, TslA, that has a reverse domain organisation. TslA is widely found across Bacillota including Staphylococcus, Enterococcus and Listeria. We show that the S. aureus TslA N-terminal domain is a phospholipase A with anti-staphylococcal activity that is neutralised by the immunity lipoprotein TilA. Two small helical partner proteins, TlaA1 and TlaA2 are essential for T7-dependent secretion of TslA and at least one of these interacts with the TslA C-terminal domain to form a helical stack. Cryo-EM analysis of purified TslA complexes indicate that they share structural similarity with canonical T7 substrates. Our findings suggest that the T7SS has the capacity to recognise a secretion signal present at either end of a substrate.
Author(s): Garrett SR, Mietrach N, Deme J, Bitzer A, Yang Y, Ulhuq FR, Kretschmer D, Heilbronner S, Smith TK, Lea SM, Palmer T
Publication type: Article
Publication status: Published
Journal: Nature Communications
Year: 2023
Volume: 14
Issue: 1
Online publication date: 19/12/2023
Acceptance date: 05/12/2023
Date deposited: 26/01/2024
ISSN (electronic): 2041-1723
Publisher: Springer Nature
URL: https://doi.org/10.1038/s41467-023-44221-y
DOI: 10.1038/s41467-023-44221-y
Data Access Statement: Other data generated or analysed in this study are available within the article and its supplementary materials. Source data are provided with this paper with the exception of the microscopy images which are available at FigShare (https://doi.org/10.6084/m9.figshare.24717864.v1). Databases used are Alphafold (https://alphafold.ebi.ac.uk/), Refseq (https://www.ncbi.nlm.nih.gov/refseq/) and Lipid maps (https://www.lipidmaps.org). Source data are provided with this paper.
PubMed id: 38114483
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