DeLeo F R, Quinn M T
Department of Veterinary Molecular Biology, Montana State University, Bozeman 59717, USA.
J Leukoc Biol. 1996 Dec;60(6):677-91. doi: 10.1002/jlb.60.6.677.
Phagocytes such as neutrophils play a key role in the body's innate immune response to infection. These cells travel throughout the body in search of pathogens and are rapidly mobilized to sites of inflammation where they phagocytose these pathogens and subsequently release a variety of toxic oxygen radical species and proteolytic enzymes to directly destroy the engulfed particle. The generation of microbicidal oxidants by neutrophils results from the action of a multi-protein enzymatic complex known as the NADPH oxidase. Altogether, there are currently seven proteins reported to be associated with the NADPH oxidase assembly. In resting neutrophils, these NADPH oxidase protein components are segregated into cytoplasmic and plasma membrane compartments. However, during assembly and activation of the NADPH oxidase, the cytosolic protein components translocate to the plasma membrane or phagosomal membrane where they assemble around a central membrane-bound protein known as flavocytochrome b. This assembly process is highly regulated and involves multiple binding interactions between the individual NADPH oxidase proteins, resulting in an active oxidase complex. Over the past few years, a number of these sites of binding interaction between the oxidase proteins have been identified, leading to a clearer understanding of the intermolecular interactions occurring among protein components during the assembly process. In addition, this information has contributed to our understanding of the roles played by each protein during the activation and assembly process. In this review, we describe the key features of each NADPH oxidase protein and then summarize our current understanding of the specific molecular interactions occurring between these proteins, focusing on the role these protein:protein binding interactions play in the NADPH oxidase assembly process.
中性粒细胞等吞噬细胞在机体对感染的固有免疫反应中起关键作用。这些细胞在全身游走以寻找病原体，并迅速被动员到炎症部位，在那里它们吞噬这些病原体，随后释放多种有毒的氧自由基和蛋白水解酶以直接破坏被吞噬的颗粒。中性粒细胞产生杀菌性氧化剂是由一种称为NADPH氧化酶的多蛋白酶复合物的作用导致的。目前总共报道有七种蛋白质与NADPH氧化酶组装相关。在静息中性粒细胞中，这些NADPH氧化酶蛋白成分被分隔在细胞质和质膜区室中。然而，在NADPH氧化酶组装和激活过程中，胞质蛋白成分会转运到质膜或吞噬体膜，在那里它们围绕一种称为黄素细胞色素b的中心膜结合蛋白组装。这个组装过程受到高度调控，涉及各个NADPH氧化酶蛋白之间的多种结合相互作用，从而形成一个活性氧化酶复合物。在过去几年中，已经确定了氧化酶蛋白之间的一些这些结合相互作用位点，从而更清楚地了解了组装过程中蛋白质成分之间发生的分子间相互作用。此外，这些信息有助于我们理解每种蛋白质在激活和组装过程中所起的作用。在这篇综述中，我们描述了每种NADPH氧化酶蛋白的关键特征，然后总结了我们目前对这些蛋白质之间发生的特定分子相互作用的理解，重点关注这些蛋白质：蛋白质结合相互作用在NADPH氧化酶组装过程中所起的作用。
