Garrett_2023_Nat.Commun_14_8438

Reference

Title : A type VII-secreted lipase toxin with reverse domain arrangement - Garrett_2023_Nat.Commun_14_8438
Author(s) : Garrett SR , Mietrach N , Deme J , Bitzer A , Yang Y , Ulhuq FR , Kretschmer D , Heilbronner S , Smith TK , Lea SM , Palmer T
Ref : Nat Commun , 14 :8438 , 2023
Abstract :

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.

PubMedSearch : Garrett_2023_Nat.Commun_14_8438
PubMedID: 38114483
Gene_locus related to this paper: staau-SAV0446

Related information

Gene_locus staau-SAV0446
Family T7SS-TslA

Citations formats

Garrett SR, Mietrach N, Deme J, Bitzer A, Yang Y, Ulhuq FR, Kretschmer D, Heilbronner S, Smith TK, Lea SM, Palmer T (2023)
A type VII-secreted lipase toxin with reverse domain arrangement
Nat Commun 14 :8438

Garrett SR, Mietrach N, Deme J, Bitzer A, Yang Y, Ulhuq FR, Kretschmer D, Heilbronner S, Smith TK, Lea SM, Palmer T (2023)
Nat Commun 14 :8438