Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Biomedicine Discovery Institute, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria 3800, Australia.
Peter MacCallum Cancer Centre, Victorian Comprehensive Cancer Centre, Melbourne, Victoria 3000, Australia.
Semin Cell Dev Biol. 2017 Dec;72:117-123. doi: 10.1016/j.semcdb.2017.07.033. Epub 2017 Jul 27.
Cytotoxic lymphocytes play a key role in immune homeostasis through elimination of virally-infected and transformed target cells. They do this by employing the potent pore-forming protein, perforin, a molecule that permits cytotoxic proteases, such as granzyme B, to enter the target cell cytoplasm. The synergistic activities of perforin and granzymes bring about the destruction of target cells in a process that is now more clearly understood as a result of structural and cellular biology. These data are helping the development of new classes of immunosuppressive molecules for use in treating immune driven disease and in enhancing the success of transplant therapies. This review focuses on structural and biological aspects of perforin function.
细胞毒性淋巴细胞通过消除病毒感染和转化的靶细胞在免疫稳态中发挥关键作用。它们通过使用有效的穿孔蛋白——穿孔素来实现这一点,这种分子允许细胞毒性蛋白酶,如颗粒酶 B,进入靶细胞质。穿孔素和颗粒酶的协同作用导致靶细胞的破坏,这一过程由于结构和细胞生物学的发展现在被更清楚地理解。这些数据正在帮助开发新类别的免疫抑制分子,用于治疗免疫驱动的疾病和提高移植治疗的成功率。本综述重点介绍穿孔素功能的结构和生物学方面。