The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Structure of a tripartite protein complex that targets toxins to the type VII secretion system
Open accessPreprint — published as 10.1073/pnas.2312455121 · Paper page
Abstract
Type VII secretion systems are membrane-embedded nanomachines used by Gram-positive bacteria to export effector proteins from the cytoplasm to the extracellular environment. Many of these effectors are polymorphic toxins comprised of an N-terminal Leu-x-Gly (LXG) domain of unknown function and a C-terminal toxin domain that inhibits the growth of bacterial competitors. In recent work, it was shown that LXG effectors require two cognate Lap proteins for T7SS-dependent export. Here, we present the 2.6Å structure of the LXG domain of the TelA toxin from the opportunistic pathogen Streptococcus intermedius in complex with both of its cognate Lap targeting factors. The structure reveals an elongated α-helical bundle within which each Lap protein makes extensive hydrophobic contacts with either end of the LXG domain. Remarkably, despite low overall sequence identity, we identify striking structural similarity between our LXG complex and PE-PPE heterodimers exported by the distantly related ESX type VII secretion systems of Mycobacteria implying a conserved mechanism of effector export among diverse Gram-positive bacteria. Overall, our findings demonstrate that LXG domains, in conjunction with their cognate Lap targeting factors, represent a tripartite secretion signal for a widespread family of T7SS toxins.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764
Flagged first, then by citations
Research works printed but not linked: 51
- 10.1111/mmi.14680 · DOI
- 10.1038/nrmicro1773 · DOI · Paper page
- 2016, The type VII secretion system of Staphylococcus aureus secretes a nuclease toxin that targets competitor bacteria, Nat Microbiol, 2, 16183, 10.1038/nmicrobiol.2016.183 · DOI
- J. C. Whitney et al., A broadly distributed toxin family mediates contact-dependent antagonism between gram-positive bacteria. eLife 6 (2017). · DOI
- 2021, Diverse LXG toxin and antitoxin systems specifically mediate intraspecies competition in Bacillus subtilis biofilms, PLoS genetics, 17, e1009682, 10.1371/journal.pgen.1009682 · DOI
- 2021, Phage infection and sub-lethal antibiotic exposure mediate Enterococcus faecalis type VII secretion system dependent inhibition of bystander bacteria, PLoS genetics, 17, e1009204, 10.1371/journal.pgen.1009204 · DOI
- 10.1073/pnas.0405620102 · DOI
- 2021, The Type VII Secretion System of Staphylococcus, Annual review of microbiology, 75, 471, 10.1146/annurev-micro-012721-123600 · DOI
- 10.1073/pnas.1322200111 · DOI
- D. Zhang , R. F. de Souza , V. Anantharaman , L. M. Iyer , L. Aravind , Polymorphic toxin systems: Comprehensive characterization of trafficking modes, processing, mechanisms of action, immunity and ecology using comparative genomics. Biology direct 7, 18 (2012). · DOI
- 10.1073/pnas.2006110117 · DOI
- 10.1128/mbio.02137-22 · DOI
- 10.1073/pnas.1119453109 · DOI
- 10.1016/j.str.2015.01.002 · DOI
- 10.1128/spectrum.01481-23 · DOI
- 10.1016/j.cell.2015.03.040 · DOI · Paper page
- 2019, Architecture of the mycobacterial type VII secretion system, Nature, 576, 321, 10.1038/s41586-019-1633-1 · DOI
- 10.1038/s41586-021-03517-z · DOI
- 10.1111/mmi.12770 · DOI
- J. Piton , F. Pojer , S. Wakatsuki , C. Gati , S. T. Cole , High resolution CryoEM structure of the ring-shaped virulence factor EspB from Mycobacterium tuberculosis. J Struct Biol X 4, 100029 (2020). · DOI
- 10.1126/science.aav5912 · DOI
- 10.1111/mmi.13575 · DOI
- 10.1101/2023.06.03.543475 · DOI
- 10.1101/2023.04.01.535202 · DOI · Paper page
- 10.1074/jbc.M112.397596 · DOI
- 10.1042/BCJ20160257 · DOI
- N. Poweleit et al., The structure of the endogenous ESX-3 secretion system. eLife 8 (2019). · DOI
- B. Warne et al., The Ess/Type VII secretion system of Staphylococcus aureus shows unexpected genetic diversity. BMC genomics 17, 222 (2016). · DOI
- 10.1099/mic.0.000650 · DOI
- K. Bowran , T. Palmer , Extreme genetic diversity in the type VII secretion system of Listeria monocytogenes suggests a role in bacterial antagonism. Microbiology (Reading ) 167 (2021). · DOI
- 2012, A novel strategy to over-express and purify homologous proteins from Streptococcus pneumoniae, Journal of biotechnology, 157, 279, 10.1016/j.jbiotec.2011.11.011 · DOI
- 10.1128/IAI.00113-10 · DOI
- 10.1016/j.str.2020.11.002 · DOI
- 10.1371/journal.pone.0013244 · DOI
- 10.1016/j.jmb.2019.03.007 · DOI
- 2006, Tricine-SDS-PAGE, Nature protocols, 1, 16, 10.1038/nprot.2006.4 · DOI
- 10.1107/S0907444906019949 · DOI
- 10.1107/S0907444909042589 · DOI
- 10.1107/S0907444910007493 · DOI · Paper page
- 2012, Towards automated crystallographic structure refinement with phenix.refine. Acta crystallographica. Section D, Biological crystallography, 68, 352, 10.1107/S0907444912001308 · DOI · Paper page
- 2022, ColabFold: making protein folding accessible to all, Nature methods, 19, 679, 10.1038/s41592-022-01488-1 · DOI · Paper page
- 10.1002/PRO.3235 · DOI · Paper page
- 1996, Lipophilicity in molecular modeling, Pharmaceutical research, 13, 335, 10.1023/A:1016024005429 · DOI
- 10.1093/nar/29.1.221 · DOI
- L. Holm , Using Dali for Protein Structure Comparison. Methods Mol Biol 2112, 29–42 (2020). · DOI
- 10.1093/nar/gkv397 · DOI
- F. Sievers et al., Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol Syst Biol 7, 539 (2011). · DOI
- T. J. Wheeler , J. Clements , R. D. Finn , Skylign: a tool for creating informative, interactive logos representing sequence alignments and profile hidden Markov models. BMC bioinformatics 15, 7 (2014). · DOI
- 10.1093/BIOINFORMATICS/BTZ921 · DOI
- 10.1126/science.1218231 · DOI · Paper page
- 10.1093/nar/gkh398 · DOI
Metadata
- Authors
- Klein, T. A., Shah, P. Y., Gkragkopoulou, P., Grebenc, D. W., Kim, Y., & Whitney, J. C.
- Affiliations
- Michael G. DeGroote Institute for Infectious Disease Research (CA)
- Argonne National Laboratory (US)
- Corresponding author
- Klein, Timothy A.
- Shah, Prakhar Y.
- Whitney, John C.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- openRxiv
- Published
- 2023-07-21
- Volume
- 121
- Issue
- 3
- Pages
- e2312455121-e2312455121
- ISSN
- 0027-8424 (ISSN-L)
- PMC
- PMC10801868
- OpenAlex
- W4390744494
- Cited by
- 28
- References
- 1
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 5 · 2023: 4
- FWCI
- 6.37
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- Funders
- U.S. Department of Energy (DE‐ AC02‐06CH11357, AC02‐06CH11357, 06CH11357, DE-AC02-)
- Burroughs Wellcome Fund (1021360)
- Government of Canada (PJT-173486)
- Office of Science (AC02‐06CH11357, DE-AC02, 06CH11357, DE-AC02-06CH11357)
- Canadian Institutes of Health Research (173486_1)
- Natural Sciences and Engineering Research Council of Canada (DE-AC02-06CH11357)
- Argonne National Laboratory (DE- AC02-06-CH11357, DE-AC02, AC02–06CH11357, 06CH11357)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
- Life Sciences › Immunology and Microbiology › Microbiology › Escherichia coli research studies
- Keywords
- type VII secretion system, Streptococcus intermedius, ESX secretion system, Mycobacterium, Gram-positive bacteria, protein complex structure
- MeSH terms
- Type VII Secretion Systems, Animals, Cytoplasm, Grasshoppers, Toxins, Biological
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
