Protein toxin complexes of Photorhabdus luminescens

• Applicant: Professor Dr. Klaus Aktories
• Subject Area: Biochemistry ; Pharmacology ; Structural Biology
• Term: from 2010 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 183175329

• Final Report Year: 2018

Final Report Abstract

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.

Publications

• 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
  (See online at 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
  (See online at 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
  (See online at 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
  (See online at 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
  (See online at 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
  (See online at https://doi.org/10.1038/srep41252)