Fig. 7: Proposed model for CROPs-mediated self-stabilization of TcsL.

In the complex extracellular environments, TcsL may exist in either open or closed conformation. TcsL in the open conformation better attacks the host cells, while the closed-form TcsL might be more resistant to autoproteolysis and degradation. The CROP-less toxin variants are sensitive to InsP6 and will easily undergo autoproteolysis and degradation. Once enter the host cell via endocytosis, the toxins undergo conformational changes in the acidic endosomes and translocate the GTD and CPD into the cytosol. Thus, the CROPs would no longer inhibit the InsP6-induced autocleavage.