Proteintoxin-Komplexe von Photorhabdus luminescens

• Antragsteller: Professor Dr. Klaus Aktories
• Fachliche Zuordnung: Biochemie ; Pharmakologie ; Strukturbiologie
• Förderung: Förderung von 2010 bis 2018
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 183175329

• Erstellungsjahr: 2018

Zusammenfassung der Projektergebnisse

The project allowed us to analyze the Photorhabdus luminescens Tc toxins in great detail. Outstanding structure analysis was done in collaboration with the laboratory of Stefan Raunser (MPI, Dortmund). We were able to identify crucial amino acid residues in the ADP-ribosyltransferase domains of the enzyme components of the toxins. We further characterized the functional consequences of the ADP-ribosylation of actin in Thr148. Moreover, we got new insights into the mechanism of toxin uptake and translocation by using toxin chimeras and compounds inhibiting specific steps of the intoxication process.

Projektbezogene Publikationen (Auswahl)

• 2014. Mechanism of Tc toxin action revealed in molecular detail. Nature. 508:61-65
  Meusch, D., C. Gatsogiannis, R.G. Efremov, A.E. Lang, O. Hofnagel, I.R. Vetter, K. Aktories, and S. Raunser
  (Siehe online unter https://doi.org/10.1038/nature13015)
• 2014. The chaperone Hsp90 and PPIases of the cyclophilin and FKBP families facilitate membrane translocation of Photorhabdus luminescens ADP-ribosyltransferases. Cell Microbiol. 16:490-503
  Lang, A.E., K. Ernst, H. Lee, P. Papatheodorou, C. Schwan, H. Barth, and K. Aktories
  (Siehe online unter https://doi.org/10.1111/cmi.12228)
• 2015. The actin and Rho-modifying toxins PTC3 and PTC5 of Photorhabdus luminescens: enzyme characterization and induction of MAL/SRF-dependent transcription. Cell Microbiol. 17:579-594
  Pfaumann, V., A.E. Lang, C. Schwan, G. Schmidt, and K. Aktories
  (Siehe online unter https://doi.org/10.1111/cmi.12386)
• 2017. Actin ADP-ribosylation at Threonine148 by Photorhabdus luminescens toxin TccC3 induces aggregation of intracellular F-actin. Cell Microbiol. 19
  Lang, A.E., Z. Qu, C. Schwan, U. Silvan, A. Unger, C.A. Schoenenberger, K. Aktories, and H.G. Mannherz
  (Siehe online unter https://doi.org/10.1111/cmi.12636)
• 2017. Insecticidal toxin complexes from Photorhabdus luminescens. Curr Top Microbiol Immunol. 402:3-23
  Sheets, J., and K. Aktories
  (Siehe online unter https://doi.org/10.1007/82_2016_55)
• 2017. Targeted delivery of an ADP-ribosylating bacterial toxin into cancer cells. Sci Rep. 7:41252
  Zahaf, N.I., A.E. Lang, L. Kaiser, C.D. Fichter, S. Lassmann, A. McCluskey, A. Augspach, K. Aktories, and G. Schmidt
  (Siehe online unter https://doi.org/10.1038/srep41252)