A High‐Affinity Calmodulin‐Binding Site in the CyaA Toxin Translocation Domain is Essential for Invasion of Eukaryotic Cells

The molecular mechanisms and forces involved in the translocation of bacterial toxins into host cells are still a matter intense research. adenylate cyclase (CyaA) toxin from Bordetella pertussis displays unique intoxication pathway which its catalytic domain is directly translocated across target cell membranes. CyaA region contains segment, P454 (residues 454–484), exhibits membrane-active properties related to antimicrobial peptides. Herein, results show that this peptide able translocate membranes interact with calmodulin (CaM). Structural biophysical analyses reveal key residues membrane destabilization binding. Mutational analysis demonstrates these play crucial role cells. In addition, calmidazolium, inhibitor, efficiently blocks internalization. It proposed after binding cells, segment destabilizes plasma membrane, translocates lipid bilayer binds calmodulin. Trapping by CaM:P454 interaction cytosol may assist entry N-terminal converting stochastic motion polypeptide chain through an efficient vectorial