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

膜攻击复合体穿孔素(MACPF)蛋白在免疫和发育过程中发挥着重要作用。这些分子共同构成了真核生物中最大的孔道形成蛋白家族。这一建议将大大提高我们对MACPF成孔机理的认识。这些数据将为蛋白质如何改变形状以及如何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反应中。最后，对MACPF蛋白质如何组装成环并在膜上打孔的详细了解将有助于这些蛋白质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.