6suq › Citations

Towards the application of Tc toxins as a universal protein translocation system.

Roderer D, Schubert E, Sitsel O, Raunser S
Nat Commun 10 5263 (2019)
Cited: 18 times
EuropePMC logo PMID: 31748551

Abstract

Tc toxins are bacterial protein complexes that inject cytotoxic enzymes into target cells using a syringe-like mechanism. Tc toxins are composed of a membrane translocator and a cocoon that encapsulates a toxic enzyme. The toxic enzyme varies between Tc toxins from different species and is not conserved. Here, we investigate whether the toxic enzyme can be replaced by other small proteins of different origin and properties, namely Cdc42, herpes simplex virus ICP47, Arabidopsis thaliana iLOV, Escherichia coli DHFR, Ras-binding domain of CRAF kinase, and TEV protease. Using a combination of electron microscopy, X-ray crystallography and in vitro translocation assays, we demonstrate that it is possible to turn Tc toxins into customizable molecular syringes for delivering proteins of interest across membranes. We also infer the guidelines that protein cargos must obey in terms of size, charge, and fold in order to apply Tc toxins as a universal protein translocation system.

Reviews citing this publication (3)

  1. Challenges and approaches to studying pore-forming proteins. Benton JT, Bayly-Jones C. Biochem Soc Trans 49 2749-2765 (2021)
  2. Nematophilic bacteria associated with entomopathogenic nematodes and drug development of their biomolecules. Awori RM. Front Microbiol 13 993688 (2022)
  3. Pore-Forming Proteins: From Pore Assembly to Structure by Quantitative Single-Molecule Imaging. Margheritis E, Kappelhoff S, Cosentino K. Int J Mol Sci 24 4528 (2023)

Articles citing this publication (15)

  1. Structure of the Lifeact-F-actin complex. Belyy A, Merino F, Sitsel O, Raunser S. PLoS Biol 18 e3000925 (2020)
  2. The evolution of SPHIRE-crYOLO particle picking and its application in automated cryo-EM processing workflows. Wagner T, Raunser S. Commun Biol 3 61 (2020)
  3. Structure of a bacterial Rhs effector exported by the type VI secretion system. Günther P, Quentin D, Ahmad S, Sachar K, Gatsogiannis C, Whitney JC, Raunser S. PLoS Pathog 18 e1010182 (2022)
  4. Genome-wide dissection reveals diverse pathogenic roles of bacterial Tc toxins. Song N, Chen L, Zhou Z, Ren X, Liu B, Zhou S, Wang C, Wu Y, Waterfield NR, Yang J, Yang G. PLoS Pathog 17 e1009102 (2021)
  5. Conformation-specific inhibitors of activated Ras GTPases reveal limited Ras dependency of patient-derived cancer organoids. Wiechmann S, Maisonneuve P, Grebbin BM, Hoffmeister M, Kaulich M, Clevers H, Rajalingam K, Kurinov I, Farin HF, Sicheri F, Ernst A. J Biol Chem 295 4526-4540 (2020)
  6. Targeted intracellular delivery of Cas13 and Cas9 nucleases using bacterial toxin-based platforms. Tian S, Liu Y, Appleton E, Wang H, Church GM, Dong M. Cell Rep 38 110476 (2022)
  7. Mechanism of threonine ADP-ribosylation of F-actin by a Tc toxin. Belyy A, Lindemann F, Roderer D, Funk J, Bardiaux B, Protze J, Bieling P, Oschkinat H, Raunser S. Nat Commun 13 4202 (2022)
  8. N-terminal signal peptides facilitate the engineering of PVC complex as a potent protein delivery system. Jiang F, Shen J, Cheng J, Wang X, Yang J, Li N, Gao N, Jin Q. Sci Adv 8 eabm2343 (2022)
  9. Thermodynamic Stability Is a Strong Predictor for the Delivery of DARPins to the Cytosol via Anthrax Toxin. Becker L, Singh Badwal J, Brandl F, Verdurmen WPR, Plückthun A. Pharmaceutics 13 1285 (2021)
  10. Native structure of mosquito salivary protein uncovers domains relevant to pathogen transmission. Liu S, Xia X, Calvo E, Zhou ZH. Nat Commun 14 899 (2023)
  11. Insecticidal Activity of Chitinases from Xenorhabdus nematophila HB310 and Its Relationship with the Toxin Complex. Liu J, Bai H, Song P, Nangong Z, Dong Z, Li Z, Wang Q. Toxins (Basel) 14 646 (2022)
  12. DARPins bind their cytosolic targets after having been translocated through the protective antigen pore of anthrax toxin. Becker L, Plückthun A. Sci Rep 13 8048 (2023)
  13. Recent insights into mechanisms of cellular toxicity and cell recognition associated with the ABC family of pore-forming toxins. Aleksandrova NA, Roche SG, Low YS, Landsberg MJ. Biochem Soc Trans 51 1235-1244 (2023)
  14. Structure and activation mechanism of the Makes caterpillars floppy 1 toxin. Belyy A, Heilen P, Hagel P, Hofnagel O, Raunser S. Nat Commun 14 8226 (2023)
  15. Structures of the Insecticidal Toxin Complex Subunit XptA2 Highlight Roles for Flexible Domains. Martin CL, Chester DW, Radka CD, Pan L, Yang Z, Hart RC, Binshtein EM, Wang Z, Nagy L, DeLucas LJ, Aller SG. Int J Mol Sci 24 13221 (2023)


Quick links