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

膜攻击复合物穿孔素（MACPF）蛋白在免疫和发育中起着至关重要的作用。这些分子共同构成真核生物中最大的孔形成蛋白家族。这一建议将导致我们对MACPF孔隙形成机制的理解取得重大进展。这些数据将为蛋白质如何改变形状并采用水溶性和膜结合状态提供基本的见解。我们的工作最终也将在开发控制不必要的MACPF功能的方法方面发挥重要作用，例如在糖尿病或移植排斥中。最后，详细了解MACPF蛋白如何组装成环并在膜上打孔将促进这些蛋白作为技术工具的发展。

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.