Department of Protein Chemistry, Genentech, 1 DNA Way, South San Francisco, CA 94080, United States.
Methods. 2012 Aug;57(4):448-58. doi: 10.1016/j.ymeth.2012.06.004. Epub 2012 Jun 19.
Approximately one quarter of all human genes encode proteins that function in the extracellular space or serve to bridge the extracellular and intracellular environments. Physical associations between these secretome proteins serve to regulate a wide range of biological activities and consequently represent important therapeutic targets. Moreover, some extracellular proteins are targeted by pathogens to allow host access or immune evasion. Despite the importance of extracellular protein-protein interactions, our knowledge in this area has remained sparse. Weak affinities and low abundance have often hindered efforts to identify these interactions using traditional methods such as biochemical purification and cDNA library expression cloning. Moreover, current large-scale protein-protein interaction mapping techniques largely under represent extracellular protein-protein interactions. This review highlights emerging biosensor and protein microarray technology, along with more traditional cell-based techniques, that are compatible with secretome-wide screens for extracellular protein-protein interaction discovery. A combination of these approaches will serve to rapidly expand our knowledge of the extracellular protein-protein interactome.
大约四分之一的人类基因编码在细胞外空间发挥作用或用于连接细胞外和细胞内环境的蛋白质。这些分泌蛋白之间的物理相互作用有助于调节广泛的生物活性，因此代表了重要的治疗靶点。此外，一些细胞外蛋白被病原体靶向，以允许宿主进入或免疫逃避。尽管细胞外蛋白-蛋白相互作用很重要，但我们在这方面的知识仍然很少。弱亲和力和低丰度常常阻碍了使用传统方法（如生化纯化和 cDNA 文库表达克隆）来识别这些相互作用的努力。此外，当前的大规模蛋白质-蛋白质相互作用图谱技术在很大程度上不能代表细胞外蛋白质-蛋白质相互作用。这篇综述强调了新兴的生物传感器和蛋白质微阵列技术，以及更传统的基于细胞的技术，这些技术与分泌组范围内发现细胞外蛋白质-蛋白质相互作用的筛选兼容。这些方法的结合将有助于快速扩展我们对细胞外蛋白质-蛋白质相互作用组的认识。
