嘌呤能受体
受体
蛋白质组学
细胞生物学
生物
小分子
计算生物学
热休克蛋白90
自噬
信号转导
膜蛋白
蛋白质组
生物化学
膜
热休克蛋白
基因
细胞凋亡
作者
Marjorie A. Carnero Corrales,Sarah Zinken,Georgios Konstantinidis,Muhammad Rafehi,Aliaa Abdelrahman,Yao‐Wen Wu,Petra Janning,Christa E. Müller,Luca Laraia,Herbert Waldmann
标识
DOI:10.1016/j.chembiol.2021.02.017
摘要
Signaling pathways are frequently activated through signal-receiving membrane proteins, and the discovery of small molecules targeting these receptors may yield insights into their biology. However, due to their intrinsic properties, membrane protein targets often cannot be identified by means of established approaches, in particular affinity-based proteomics, calling for the exploration of new methods. Here, we report the identification of indophagolin as representative member of an indoline-based class of autophagy inhibitors through a target-agnostic phenotypic assay. Thermal proteome profiling and subsequent biochemical validation identified the purinergic receptor P2X4 as a target of indophagolin, and subsequent investigations suggest that indophagolin targets further purinergic receptors. These results demonstrate that thermal proteome profiling may enable the de novo identification of membrane-bound receptors as cellular targets of bioactive small molecules.
科研通智能强力驱动
Strongly Powered by AbleSci AI