Crystal structure of the Clostridium limosum C3 exoenzyme

Abstract

C3-like toxins ADP-ribosylate and inactivate Rho GTPases. Seven C3-like ADP-ribosyltransferases produced by Clostridium botulinum, Clostridium limosum, Bacillus cereus and Staphylococcus aureus were identified and two representatives – C3bot from C. botulinum and C3stau2 from S. aureus – were crystallized. Here we present the 1.8 A˚ structure of C. limosum C3 transferase C3lim and compare it to the structures of other family members. In contrast to the structure of apoC3bot, the canonical ADP-ribosylating turn turn motif is observed in a primed conformation, ready for NAD binding. This suggests an impact on the binding mode of NAD and on the transferase reaction. The crystal structure explains why autoADP-ribosylation of C3lim at Arg41 interferes with the ADPribosyltransferase activity of the toxin.