Structural investigation of protein:protein interactions within the membrane attack complex of complement

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Our aim is to find out why some people are susceptible to bacterial infections, such as meningitis.When our immune system detects the presence of infecting organisms, it triggers a rapid response to find, kill and remove the organisms. Complement is the name of one arm of our immune system and a remarkable feature of the complement response is its ability to kill organisms by piercing their cell membranes with many large holes, causing them to leak. These holes are made of five different proteins that rapidly self-assemble in an organised manner to form tube-like pores, called Membrane Attack Complexes (MAC), that pass through the cell membranes.We are making the component parts of MAC proteins separately to determine their individual shapes and chemical characteristics, and to work out how they fit together. We aim to discover what features are important for the process of the MAC assembly and for maintaining a stable pore. Then we can determine how to stimulate, or to suppress, the assembly and stability of the pores.This knowledge can be used to guide the design of drugs either to fight bacterial infections or to prevent unwanted complement attack, for example in auto-immune diseases, where a person’s immune system attacks their own body, or after transplant surgery to prevent organ rejection.