Gros Piet, Milder Fin J, Janssen Bert J C
Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, Netherlands.
Nat Rev Immunol. 2008 Jan;8(1):48-58. doi: 10.1038/nri2231.
Complement in mammalian plasma recognizes pathogenic, immunogenic and apoptotic cell surfaces, promotes inflammatory responses and marks particles for cell lysis, phagocytosis and B-cell stimulation. At the heart of the complement system are two large proteins, complement component C3 and protease factor B. These two proteins are pivotal for amplification of the complement response and for labelling of the target particles, steps that are required for effective clearance of the target. Here we review the molecular mechanisms of complement activation, in which proteolysis and complex formation result in large conformational changes that underlie the key offensive step of complement executed by C3 and factor B. Insights into the mechanisms of complement amplification are crucial for understanding host defence and pathogen immune evasion, and for the development of complement-immune therapies.
哺乳动物血浆中的补体可识别致病性、免疫原性和凋亡细胞表面，促进炎症反应，并标记颗粒以进行细胞裂解、吞噬作用和B细胞刺激。补体系统的核心是两种大蛋白，即补体成分C3和蛋白酶因子B。这两种蛋白对于补体反应的放大以及靶颗粒的标记至关重要，而这些步骤是有效清除靶标的必要条件。在这里，我们综述补体激活的分子机制，其中蛋白水解和复合物形成导致大的构象变化，这些变化是由C3和因子B执行的补体关键攻击步骤的基础。深入了解补体放大机制对于理解宿主防御和病原体免疫逃逸以及补体免疫疗法的开发至关重要。
