The mechanism for Tse5 toxic behavior at model cellular membranes

Pseudomonas aeruginosa, a harmful bacterium, uses a system called T6SS to inject special proteins into nearby cells, giving it an advantage during infections. However, very little is known about the mechanism of action of these proteins. In our research, we will uncover how one of these proteins, called Tse5, operates. We hypothetise that Tse5 acts as a carrier of a pore-forming toxin, creating small channels in cell membranes that cause cell depolarisation and eventually cell death. The protein is composed by 3 sub-domains, one that acts as a shell and adsorbs to the surface of the membrane. Meanwhile, a hydrophobic sub-domain hidden inside of the shell moves and inserts into the membrane. In this process a pore or channel is proposed to form which causes its toxicity. We will use Neutron Reflection (NR) data to validate this hypothesis based on crystallography, electric measurements and MD simulations, since no other method can provide such detailed structural information. This experiment will enable how Tse5 adsorbs to the surface and whether the toxin gets inside of the core of the lipid membrane.