Institute of Biosciences and Technology, College of Medicine, Texas A&M University, Houston, TX, 77030, USA.
Department of Translational Medical Sciences, College of Medicine, Texas A&M University, Houston, TX, 77030, USA.
Adv Biol (Weinh). 2021 May;5(5):e2000147. doi: 10.1002/adbi.202000147. Epub 2020 Dec 30.
The spatiotemporal organization of oligomeric protein complexes, such as the supramolecular organizing centers (SMOCs) made of MyDDosome and MAVSome, is essential for transcriptional activation of host inflammatory responses and immunometabolism. Light-inducible assembly of MyDDosome and MAVSome is presented herein to induce activation of nuclear factor-kB and type-I interferons. Engineering of SMOCs and the downstream transcription factor permits programmable and customized innate immune operations in a light-dependent manner. These synthetic molecular tools will likely enable optical and user-defined modulation of innate immunity at a high spatiotemporal resolution to facilitate mechanistic studies of distinct modes of innate immune activations and potential intervention of immune disorders and cancer.
寡聚蛋白复合物的时空组织，如由 MyDDosome 和 MAVSome 组成的超分子组织中心 (SMOCs)，对于宿主炎症反应和免疫代谢的转录激活至关重要。本文提出了诱导 MyDDosome 和 MAVSome 光诱导组装的方法，以诱导核因子-kB 和 I 型干扰素的激活。SMOCs 和下游转录因子的工程化使得以光依赖的方式进行可编程和定制的固有免疫操作成为可能。这些合成分子工具可能会实现对固有免疫的高时空分辨率的光学和用户定义的调节，以促进对固有免疫激活的不同模式的机制研究，并为免疫紊乱和癌症的潜在干预提供帮助。
