Structural and Functional studies on Membrane Attack Complex / Perforin-like proteins

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Membrane Attack Complex Perforin (MACPF) proteins play crucial roles in immunity and development. Together, these molecules comprise the largest family of pore forming proteins in eukaryotes. This proposal will result in a major advancement of knowledge in our understanding of the MACPF mechanism of pore formation. These data will provide fundamental insight into how proteins can change shape and adopt both water-soluble and membrane bound states. Our work will also eventually be important in developing approaches to control unwanted MACPF function, for example in diabetes or transplant rejection. Finally, a detailed understanding of how MACPF proteins assemble into rings and punch holes in membranes will facilitate the development of these proteins as technological tools.