The signature feature of mammalian complement is the ability to kill invading cells by puncturing their plasma membranes. This assault is carried out by the Membrane Attack Complex (MAC), which is a large protein complex composed of 5 different serum proteins. Very little is known about the process of MAC assembly, the structure of the fully-assembled MAC, or even of the 3D structures of the individual constituent MAC proteins. The long-term goal of the Ogata laboratory studies is to obtain a better picture of the MAC: how the individual proteins are arranged in the complex, what forces drive independent soluble serum proteins to aggregate into the membrane-bound MAC, and how this process is regulated. This information should allow us to begin to fashion a molecular model of MAC assembly and structure. With respect to human disease, the MAC is best known for its defense against infection by foreign cells, but it can attack and injure host cells as well. For example, MAC attack on host cells has been identified as a major contributor to the vascular complications of diabetes, the inflammatory pathogenesis of atherosclerosis, and age-related macular degeneration. A clearer picture of the MAC will provide insights into the design of drugs that control MAC assembly and injury in these prevalent and devastating human diseases.

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