Project Title: Bacterial secretion systems
Summary: The bacterial type II secretion system (T2SS) is a sophisticated molecular machine consisting of multiple copies of at least 12 different proteins. It exports the lytic enzymes that destroy plant tissue and toxins that cause disease and death in humans. The T2SS is thought to function by a piston mechanism in which a short pilus is assembled and then disassembled for each protein molecule secreted. This complex, two-membrane spanning, machine comprises the following four sub-assemblies:
- A secretion ATPase providing the energy for secretion on the cytoplasmic side of the inner membrane, which is closely associated with;
- A sophisticated Inner Membrane Platform, which senses the presence of a protein to be secreted and assembles;
- The Pseudopilus in the space between the membranes, whose tip pushes secreted proteins through;
- The large gated pore of the Outer Membrane Complex.
In this project we shall determine much more about the structure and organisation of the proteins that form the Inner Membrane Platform and govern the interactions with the Outer Membrane Complex and with proteins to be secreted. This understanding may allow us to develop methods of halting secretion and preventing destruction of crops and foodstuffs as well as protecting humans against infection. Bacteria with T2SS are the causative agents of: cholera, children’s diarrhea, and respiratory infection, which is potentially fatal in the immunocompromised. Hence our studies are of potential relevance for a range of crucially important multi-protein membrane-spanning machineries occurring in a wide variety of pathogenic bacteria.