A type VII-secreted lipase toxin with reverse domain arrangement.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
19 Dec 2023
19 Dec 2023
Historique:
received:
03
08
2023
accepted:
05
12
2023
medline:
20
12
2023
pubmed:
20
12
2023
entrez:
19
12
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 38114483
doi: 10.1038/s41467-023-44221-y
pii: 10.1038/s41467-023-44221-y
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
8438Subventions
Organisme : Wellcome Trust (Wellcome)
ID : 10183/Z/15/Z
Organisme : Wellcome Trust (Wellcome)
ID : 224151/Z/21/Z
Organisme : Deutsches Zentrum für Infektionsforschung (German Center for Infection Research)
ID : TTU 08.708
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : M2871/1-1
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : EXC 2124 - 390838134
Organisme : RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)
ID : BB/M011186/1
Informations de copyright
© 2023. The Author(s).
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