Glucose as a Protein-Condensing Cellular Solute
Glucose as a Protein-Condensing Cellular Solute
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葡萄糖作为蛋白质浓缩细胞溶质
DOI：
10.1021/acschembio.1c00849
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发表时间：
2022
期刊：
影响因子：
4
通讯作者：
M.
中科院分区：
文献类型：
--
作者：
Noda;N.;Jung;Y.;Ado;G.;Mizuhata;Y.;Higuchi;M.;Ogawa;T.;Ishidate;F.;Sato;S.;Kurata;H.;Tokitoh;N.;Uesugi;M.
本研究报告了一个令人惊讶的蛋白质浓缩效果的葡萄糖，提示我们的意外观察过程中的化学库筛选在高糖条件下。我们注意到某些化合物的“葡萄糖化”，其中生理浓度的葡萄糖诱导化合物聚集。我们的蛋白质组学分析确定了三种细胞蛋白（钙调蛋白，rho鸟嘌呤核苷酸交换因子40和聚泛素-C），它们显示出强大的葡萄糖依赖性沉淀。这些蛋白质之一，钙调蛋白，形成葡萄糖依赖性的缩合物，控制肝细胞中的细胞糖原分解。我们的研究结果表明，葡萄糖是一个迄今未被充分认识的驱动程序的蛋白质相分离，可能有深远的影响细胞内稳态。
The present study reports a surprising protein-condensing effect of glucose, prompted by our accidental observation during chemical library screening under a high-glucose condition. We noticed “glucosing-out” of certain compounds, in which physiological concentrations of glucose induced compound aggregation. Adapting the “glucosing-out” concept to proteins, our proteomic analysis identified three cellular proteins (calmodulin, rho guanine nucleotide exchange factor 40, and polyubiquitin-C) that displayed robust glucose-dependent precipitation. One of these proteins, calmodulin, formed glucose-dependent condensates that control cellular glycogenolysis in hepatic cells. Our findings suggest that glucose is a heretofore underappreciated driver of protein phase separation that may have profound effects on cellular homeostasis.