Struktur-Funktionsanalyse "großer" clostridialer Zytotoxine

• Antragsteller: Professor Dr. Klaus Aktories
• Fachliche Zuordnung: Pharmakologie ; Parasitologie und Biologie der Erreger tropischer Infektionskrankheiten
• Förderung: Förderung von 2004 bis 2018
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 5437441

• Erstellungsjahr: 2018

Zusammenfassung der Projektergebnisse

Taken together, the project allowed us to identify the cell membrane receptor of the large clostridial glucosylating toxin TpeL. This study was paradigmatic for the concept that not only one but more than one membrane receptors are involved in up-take of clostridial glucosylating toxins. Moreover, we analyzed the action of Tpel on oncogenic Ras signaling and specified the cell receptor by engineering chimeric toxins. Finally, we were able to identify the chaperonin TRiC/CCT complex as an essential factor involved in the up-take of glucosylating toxins. We thank the DFG for supporting our studies.

Projektbezogene Publikationen (Auswahl)

• LRP1 is a receptor for Clostridium perfringens TpeL toxin indicating a two-receptor model of clostridial glycosylating toxins. Proc Natl Acad Sci USA. 2014; 111: 6431-6
  Schorch B, Song S, van Diemen FR, Bock HH, May P, Herz J, Brummelkamp TR, Papatheodorou P, Aktories K
  
• Bacterial glycosyltransferase toxins. Cell Microbiol. 2015; 17: 1752-65
  Jank T, Belyi Y, Aktories K
  
• Novel receptors for bacterial protein toxins. Curr Opin Microbiol. 2015; 23C: 55-61
  Schmidt G, Papatheodorou P, Aktories K
  
• Rho-modifying bacterial protein toxins. Pathog Dis. 2015; 73: ftv091
  Aktories K
  
• Clostridium difficile Toxin Biology. Annu Rev Microbiol. 2017; 71: 281-307
  Aktories K, Schwan C, Jank T
  
• 2018. Strongly enhanced colorectal cancer risk stratification by combining family history and genetic risk score. Clinical epidemiology, 10 143 143–152
  Steinemann M, Andreas Schlosser A, Thomas Janka T , Aktories K
  
• Targeting oncogenic Ras by the Clostridium perfringens toxin TpeL. Oncotarget. 2018; 9: 16489-500
  Schorch B, Heni H, Zahaf NI, Brummer T, Mione M, Schmidt G, Papatheodorou P, Aktories K