The complement system is a humoral immuno-effector system present in blood plasma that consists of about 20 plasma proteins. The final outcome of complement activation is the formation of the membrane attack complex (MAC) on target cell membranes. The MAC assembles by the sequential fusion of five hydrophilic proteins (C5b through C9) to form an integral transmembrane pore complex. The focus of this grant proposal is the investigation of the structures and functions of two of the five proteins that comprise the MAC, namely C6 and C7, Since a transition from a soluble state to a membrane bound intermediate occurs after C7 adds to C5b-6, the studies on C6 and C7 provide an opportunity to discern the molecular mechanism of membrane binding and penetration by the late acting proteins of complement. The scope of proposed research calls for obtaining structural information about C6,C7 and their complexes at several levels of organization. The immediate priority is to complete the important regions in these proteins that are involved in subunit interaction and membrane binding. The outcome of this research should provide a detailed account of the early events in the assembly of the MAC.
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