The largest family of pore forming proteins in eukaryote organisms is the membrane attack complex / perforin (MACPF) superfamily. In animals these molecules perform crucial roles in immunity and developmental biology. In this proposal we aim to investigate how MACPF proteins are recruited to the cell membranes and how these molecules interact with receptors and lipids. We will initiate structural studies on the pore or pre-pore form of a MACPF protein. Together the work will permit a molecular understanding of how MACPF proteins recognize target cells and how these molecules change shape during pore formation. We anticipate these data will eventually permit development of approaches to control MACPF function