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A type VII-secreted lipase toxin with reverse domain arrangement
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dc.contributor.author | Garrett, Stephen R. | |
dc.contributor.author | Mietrach, Nicole | |
dc.contributor.author | Deme, Justin | |
dc.contributor.author | Bitzer, Alina | |
dc.contributor.author | Yang, Yaping | |
dc.contributor.author | Ulhuq, Fatima R. | |
dc.contributor.author | Kretschmer, Dorothee | |
dc.contributor.author | Heilbronner, Simon | |
dc.contributor.author | Smith, Terry K. | |
dc.contributor.author | Lea, Susan M. | |
dc.contributor.author | Palmer, Tracy | |
dc.date.accessioned | 2023-12-20T11:30:12Z | |
dc.date.available | 2023-12-20T11:30:12Z | |
dc.date.issued | 2023-12-19 | |
dc.identifier | 297535227 | |
dc.identifier | 1ee6a654-fe93-49f1-b7e7-7adfda7622dd | |
dc.identifier | 85180203557 | |
dc.identifier.citation | Garrett , S R , Mietrach , N , Deme , J , Bitzer , A , Yang , Y , Ulhuq , F R , Kretschmer , D , Heilbronner , S , Smith , T K , Lea , S M & Palmer , T 2023 , ' A type VII-secreted lipase toxin with reverse domain arrangement ' , Nature Communications , vol. 14 , 8438 . https://doi.org/10.1038/s41467-023-44221-y | en |
dc.identifier.issn | 2041-1723 | |
dc.identifier.other | Jisc: 1604214 | |
dc.identifier.other | publisher-id: s41467-023-44221-y | |
dc.identifier.other | manuscript: 44221 | |
dc.identifier.uri | https://hdl.handle.net/10023/28908 | |
dc.description | Funding: This study was supported by the Wellcome Trust (through Investigator Awards 10183/Z/15/Z and 224151/Z/21/Z to TP), the Intramural Research Program of the NIH, NCI, Center for Cancer Research (awarded to SML), the German Centre of Infection Research (DZIF) to SH (TTU 08.708). NM holds a Walter Benjamin Fellowship (M2871/1-1), funded by the DFG (German Research Foundation). Additionally, we acknowledge infrastructural funding by the DFG in the frame of Germany's Excellence Strategy—EXC 2124—390838134 (SH). SG is funded by the Newcastle-Liverpool-Durham BBSRC DTP2 Training Grant, project reference number BB/M011186/1 and YY by the China Scholarship Council. | en |
dc.description.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. | |
dc.format.extent | 16 | |
dc.format.extent | 4425712 | |
dc.language.iso | eng | |
dc.relation.ispartof | Nature Communications | en |
dc.subject | QH301 Biology | en |
dc.subject | DAS | en |
dc.subject.lcc | QH301 | en |
dc.title | A type VII-secreted lipase toxin with reverse domain arrangement | en |
dc.type | Journal article | en |
dc.contributor.institution | University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis | en |
dc.contributor.institution | University of St Andrews. Biomedical Sciences Research Complex | en |
dc.contributor.institution | University of St Andrews. School of Biology | en |
dc.identifier.doi | 10.1038/s41467-023-44221-y | |
dc.description.status | Peer reviewed | en |
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