Gram negative pathogenic bacteria utilize the Type III secretion system (T3SS) for the direct deposition of effector proteins into eukaryotic cell cytoplasm to modulate their immune response. Recently it was shown that Bordetella Pertussis, the causative agent of the Pertussis disease and one of the leading causes of death worldwide in infants under the age of 5, utilizes the T3SS for virulent activity and immune modulation purposes. BteA/BopC, a 69kDa protein was shown to be secreted in a T3SS dependent manner, to target the eukaryotic lipid rafts via its N-terminal domain and to be highly toxic to mammalian cell line. The role of BteA and it’s interacting host partners are unknown and thus far no homologues were identified in the protein databases. Here we present the first glimpse on a conserved domain over many effectors and toxins. We used many biophysical techniques including NMR, X-ray crystallography and others to determine the structure of BteA N-terminal domain. This domain is also the main interaction site for BtcA, the BteA cognate chaperone. With SAXS and EPR we could determine the interaction mode of BteA with the eukaryotic membrane. Together, these results hint toward the role of BtcA beyond the T3SS secretion and in the future will enable drug development against our conserved membrane binding site.
