Merck Center for Catalysis, Princeton University, Princeton, NJ 08544, USA.
Chem Soc Rev. 2021 Mar 7;50(5):2911-2926. doi: 10.1039/d0cs01366h. Epub 2021 Jan 18.
The interactions of biomolecules underpin all cellular processes, and the understanding of their dynamic interplay can lead to significant advances in the treatment of disease through the identification of novel therapeutic strategies. Protein-protein interactions (PPIs) in particular play a vital role within this arena, providing the basis for the majority of cellular signalling pathways. Despite their great importance, the elucidation of weak or transient PPIs that cannot be identified by immunoprecipitation remains a significant challenge, particularly in a disease relevant cellular environment. Recent approaches towards this goal have utilized the in situ generation of high energy intermediates that cross-link with neighboring proteins, providing a snapshot of the biomolecular makeup of the local area or microenvironment, termed the interactome. In this tutorial review, we discuss these reactive intermediates, how they are generated, and the impact they have had on the discovery of new biology. Broadly, we believe this strategy has the potential to significantly accelerate our understanding of PPIs and how they affect cellular physiology.
生物分子的相互作用是所有细胞过程的基础，理解它们的动态相互作用可以通过确定新的治疗策略，为疾病的治疗带来重大进展。特别是蛋白质-蛋白质相互作用 (PPIs) 在这一领域中起着至关重要的作用，为大多数细胞信号通路提供了基础。尽管它们非常重要，但对于无法通过免疫沉淀鉴定的弱或瞬时 PPI 的阐明仍然是一个重大挑战，特别是在与疾病相关的细胞环境中。最近的研究方法利用了原位生成的高能中间体与邻近蛋白质交联，提供了局部区域或微环境的生物分子组成的快照，称为相互作用组。在本教程综述中，我们讨论了这些反应中间体，它们是如何产生的，以及它们对新生物学发现的影响。总的来说，我们相信这种策略有可能大大加速我们对 PPI 及其对细胞生理学影响的理解。
