Institute of Molecular Systems Biology & Department of Health Sciences and Technology, ETH Zürich, Zürich, Switzerland.
Institute of Molecular Systems Biology & Department of Health Sciences and Technology, ETH Zürich, Zürich, Switzerland.
Curr Opin Chem Biol. 2019 Feb;48:26-33. doi: 10.1016/j.cbpa.2018.09.020. Epub 2018 Oct 9.
The reductionist view of 'one target-one drug' has fueled the development of therapeutic agents to treat human disease. However, many compounds that have efficacy in vitro are inactive in complex in vivo systems. It has become clear that a molecular understanding of signaling networks is needed to address disease phenotypes in the human body. Protein signaling networks function at the molecular level through information transfer via protein-protein interactions. Cell surface exposed proteins, termed the surfaceome, are the gatekeepers between the intra- and extracellular signaling networks, translating extracellular cues into intracellular responses and vice versa. As 66% of drugs in the DrugBank target the surfaceome, these proteins are a key source for potential diagnostic and therapeutic agents. In this review article, we will discuss current knowledge about the spatial organization and molecular interactions of the surfaceome and provide a perspective on the technologies available for studying the extracellular surfaceome interaction network.
“一个靶点一种药物”的简化观点推动了治疗人类疾病的治疗剂的发展。然而，许多在体外有效的化合物在复杂的体内系统中是无效的。很明显，需要对信号网络的分子理解来解决人体中的疾病表型。蛋白质信号网络通过蛋白质-蛋白质相互作用的信息传递在分子水平上发挥作用。细胞表面暴露的蛋白质，称为表面组，是细胞内和细胞外信号网络之间的守门员，将细胞外线索转化为细胞内反应，反之亦然。由于 66%的 DrugBank 药物靶向表面组，这些蛋白质是潜在诊断和治疗剂的关键来源。在这篇综述文章中，我们将讨论关于表面组的空间组织和分子相互作用的现有知识，并提供研究细胞外表面组相互作用网络的可用技术的视角。
