Structure-function analysis of large clostridial cytotoxins

• Applicant: Professor Dr. Klaus Aktories
• Subject Area: Pharmacology ; Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2004 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5437441

• Final Report Year: 2018

Final Report Abstract

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.

Publications

• 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
  (See online at https://doi.org/10.1073/pnas.1323790111)
• Bacterial glycosyltransferase toxins. Cell Microbiol. 2015; 17: 1752-65
  Jank T, Belyi Y, Aktories K
  (See online at https://doi.org/10.1111/cmi.12533)
• Novel receptors for bacterial protein toxins. Curr Opin Microbiol. 2015; 23C: 55-61
  Schmidt G, Papatheodorou P, Aktories K
  (See online at https://doi.org/10.1016/j.mib.2014.11.003)
• Rho-modifying bacterial protein toxins. Pathog Dis. 2015; 73: ftv091
  Aktories K
  (See online at https://doi.org/10.1093/femspd/ftv091)
• Clostridium difficile Toxin Biology. Annu Rev Microbiol. 2017; 71: 281-307
  Aktories K, Schwan C, Jank T
  (See online at https://doi.org/10.1146/annurev-micro-090816-093458)
• 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
  (See online at https://doi.org/10.1073/pnas.1807658115)
• 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
  (See online at https://dx.doi.org/10.18632%2Foncotarget.24740)