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  • The EMBO Journal (2007) 26, 2552 - 2561
  • doi:10.1038/sj.emboj.7601700

Published online: 26 April 2007

Autoprocessing of the Vibrio cholerae RTX toxin by the cysteine protease domain

Kerri-Lynn Sheahan1,a, Christina L Cordero1 and Karla J Fullner Satchell1

  1. Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

Correspondence to:

Karla J Fullner Satchell, Department of Microbiology-Immunology, Northwestern University, 303 E. Chicago Avenue, Tarry 3-713, Chicago, IL 60611, USA. Tel.: +1 312 503 2162; Fax: +1 312 503 1339; E-mail: k-satchell@northwestern.edu

aPresent address: Department of Microbiology, Tufts University, 136 Harrison Avenue, Boston, MA 02111, USA

Received 30 June 2006; Accepted 30 March 2007

Vibrio cholerae RTX is a large multifunctional bacterial toxin that causes actin crosslinking. Due to its size, it was predicted to undergo proteolytic cleavage during translocation into host cells to deliver activity domains to the cytosol. In this study, we identified a domain within the RTX toxin that is conserved in large clostridial glucosylating toxins TcdB, TcdA, TcnA, and TcsL; putative toxins from V. vulnificus, Yersinia sp., Photorhabdus sp., and Xenorhabdus sp.; and a filamentous/hemagglutinin-like protein FhaL from Bordetella sp. In vivo transfection studies and in vitro characterization of purified recombinant protein revealed that this domain from the V. cholerae RTX toxin is an autoprocessing cysteine protease whose activity is stimulated by the intracellular environment. A cysteine point mutation within the RTX holotoxin attenuated actin crosslinking activity suggesting that processing of the toxin is an important step in toxin translocation. Overall, we have uncovered a new mechanism by which large bacterial toxins and proteins deliver catalytic activities to the eukaryotic cell cytosol by autoprocessing after translocation.

  • Keywords:

    • Clostridium difficile Toxin B,
    • cysteine protease,
    • GTP,
    • HCV NS2,
    • V. cholerae RTX toxin