A systems chemoproteomic analysis of acyl-CoA signaling networks

Acyl-CoAs are essential for life. These metabolites serve as fundamental cellular building blocks in the biosynthesis of lipids, intermediates in energy production via the TCA cycle, and essential precursors for reversible protein acetylation. Each of these roles are dependent on acyl-CoA/protein interactions, physical contacts that can regulate protein function via a variety of mechanisms. We utilized systems-level analyses to characterize novel protein networks that interact with metabolic acyl-CoAs, and evaluate the potential of these interactions to facilitate enzyme activity or non-enzymatic acylation. Our studies provide a roadmap for integrating chemoproteomic data with systems biology analysis, and establish a novel resource for understanding the diverse signaling roles of acyl-CoAs in biology and disease.

酰基辅酶A（Acyl-CoA）类分子是生命活动不可或缺的核心物质。这类代谢物在脂质生物合成中作为基础细胞结构单元，在通过三羧酸循环（TCA cycle）进行的能量产生过程中充当中间产物，同时亦是可逆蛋白质乙酰化反应的必需前体。上述每一项功能均依赖于酰基辅酶A与蛋白质的相互作用——这种物理接触可通过多种机制调控蛋白质的功能。本研究采用系统级分析方法，对与代谢性酰基辅酶A相互作用的新型蛋白质网络进行表征，并评估了此类相互作用促进酶活性或非酶促酰化反应的潜力。本研究为整合化学蛋白质组学（chemoproteomic）数据与系统生物学（systems biology）分析提供了可行路线图，并为阐明酰基辅酶A在生理及疾病进程中多样的信号调控功能搭建了全新的研究资源。