Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA USA; Department of Genetics, Harvard Medical School, Boston, MA, USA.
Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA USA; Department of Genetics, Harvard Medical School, Boston, MA, USA; GIGA-R, University of Liège, Liège, Belgium.
Curr Opin Struct Biol. 2017 Jun;44:201-210. doi: 10.1016/j.sbi.2017.05.003. Epub 2017 May 30.
Proteins effect a number of biological functions, from cellular signaling, organization, mobility, and transport to catalyzing biochemical reactions and coordinating an immune response. These varied functions are often dependent upon macromolecular interactions, particularly with other proteins. Small-scale studies in the scientific literature report protein-protein interactions (PPIs), but slowly and with bias towards well-studied proteins. In an era where genomic sequence is readily available, deducing genotype-phenotype relationships requires an understanding of protein connectivity at proteome-scale. A proteome-scale map of the protein-protein interaction network provides a global view of cellular organization and function. Here, we discuss a summary of methods for building proteome-scale interactome maps and the current status and implications of mapping achievements. Not only do interactome maps serve as a reference, detailing global cellular function and organization patterns, but they can also reveal the mechanisms altered by disease alleles, highlight the patterns of interaction rewiring across evolution, and help pinpoint biologically and therapeutically relevant proteins. Despite the considerable strides made in proteome-wide mapping, several technical challenges persist. Therefore, future considerations that impact current mapping efforts are also discussed.
蛋白质具有多种生物学功能，包括细胞信号转导、组织、运动和运输，以及催化生化反应和协调免疫反应。这些不同的功能通常依赖于大分子相互作用，特别是与其他蛋白质的相互作用。科学文献中的小规模研究报告了蛋白质-蛋白质相互作用（PPIs），但速度缓慢，而且偏向于研究充分的蛋白质。在基因组序列易于获取的时代，推断基因型-表型关系需要了解蛋白质在蛋白质组规模上的连接性。蛋白质-蛋白质相互作用网络的蛋白质组规模图谱提供了细胞组织和功能的全局视图。在这里，我们讨论了构建蛋白质组规模相互作用图谱的方法的总结，以及图谱绘制成就的现状和意义。相互作用图谱不仅可以作为参考，详细说明全局细胞功能和组织模式，还可以揭示疾病等位基因改变的机制，突出进化过程中相互作用重排的模式，并帮助确定具有生物学和治疗意义的蛋白质。尽管在蛋白质组范围内的映射方面取得了相当大的进展，但仍存在一些技术挑战。因此，还讨论了对当前映射工作有影响的未来考虑因素。
